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Proteinuria

MedGen UID:
10976
Concept ID:
C0033687
Disease or Syndrome
Synonyms: Proteinurias
SNOMED CT: Proteinuria (29738008); Abnormal presence of protein in urine (29738008)
 
HPO: HP:0000093

Definition

abnormal presence of protein in urine [from CHV]

Conditions with this feature

Fabry's disease
MedGen UID:
8083
Concept ID:
C0002986
Disease or Syndrome
Fabry disease results from deficient activity of the enzyme a-galactosidase (a-Gal A) and progressive lysosomal deposition of globotriaosylceramide (GL-3) in cells throughout the body. The classic form, occurring in males with less than 1% a-Gal A enzyme activity, usually has its onset in childhood or adolescence with periodic crises of severe pain in the extremities (acroparesthesias), the appearance of vascular cutaneous lesions (angiokeratomas), sweating abnormalities (anhydrosis, hypohydosis, and rarely hyperhidrosis), characteristic corneal and lenticular opacities, and proteinuria. Gradual deterioration of renal function to end-stage renal disease (ESRD) usually occurs in men in the third to fifth decade. In middle age, most males successfully treated for ESRD develop cardiac and/or cerebrovascular disease, a major cause of morbidity and mortality. Heterozygous females typically have milder symptoms at a later age of onset than males. Rarely, they may be relatively asymptomatic throughout a normal life span or may have symptoms as severe as those observed in males with the classic phenotype. In contrast, males with greater than 1% a-Gal A activity may have either (1) a cardiac variant phenotype that usually presents in the sixth to eighth decade with left ventricular hypertrophy, mitral insufficiency and/or cardiomyopathy, and proteinuria, but without ESRD; or (2) a renal variant phenotype, associated with ESRD but without the skin lesions or pain.
Cystinosis
MedGen UID:
1207
Concept ID:
C0010690
Disease or Syndrome
Nephropathic cystinosis in untreated children is characterized by renal tubular Fanconi syndrome, poor growth, hypophosphatemic rickets, impaired glomerular function resulting in complete glomerular failure, and accumulation of cystine crystals in almost all cells, leading to cellular destruction and tissue dysfunction. The typical untreated child has short stature, light complexion, rickets, and photophobia. Failure to thrive is generally noticed after approximately age six months; signs of renal tubular Fanconi syndrome (polyuria, polydipsia, dehydration, and acidosis) appear as early as age six months; corneal crystals can be present before age one year and are always present after age 16 months. Prior to the use of renal transplantation and cystine-depleting therapy, the life span in nephropathic cystinosis was no longer than ten years. With these therapies, affected individuals can survive at least into the mid-forties or fifties with satisfactory quality of life. Intermediate cystinosis is characterized by all the typical manifestations of nephropathic cystinosis, but onset is at a later age. Renal glomerular failure occurs in all untreated affected individuals, usually between ages 15 and 25 years. The non-nephropathic (ocular) form of cystinosis is characterized only by photophobia resulting from corneal cystine crystal accumulation.
Fanconi syndrome
MedGen UID:
4653
Concept ID:
C0015624
Disease or Syndrome
A genetic or acquired disorder characterized by impairment of the function of the proximal tubules of the kidney. It results in decreased reabsorption of electrolytes, glucose, amino acids, and other nutrients.
Berger disease
MedGen UID:
9032
Concept ID:
C0017661
Disease or Syndrome
End-stage renal disease (ESRD) is a major public health problem, affecting 1 in 1,000 individuals and with an annual death rate of 20% despite dialysis treatment. IgA nephropathy (IgAN) is the most common form of glomerulonephritis, a principal cause of ESRD worldwide, affecting up to 1.3% of the population. Kidneys of patients with IgA nephropathy show deposits of IgA-containing immune complexes with proliferation of the glomerular mesangium. Typical clinical features include onset before age 40 with hematuria and proteinuria, and episodes of gross hematuria following mucosal infections are common; 30% of patients develop progressive renal failure. Although not generally considered a hereditary disease, striking ethnic variation in prevalence (Julian et al., 1985; D'Amico, 1987) and familial clustering (Scolari et al., 1999), along with subclinical renal abnormalities among relatives of cases, suggest a genetic component (Gharavi et al., 2000). Genetic Heterogeneity of IgA Nephropathy A locus for familial IgA nephropathy, called IGAN1, on 6q22-q23, was described by Gharavi et al. (2000). Another locus, IGAN2 (613944), was identified by Paterson et al. (2007) on chromosome 2q36. Polymorphisms in the ACE (106180) and AGT (106150) genes have been associated with progression to chronic renal failure in patients with IgA nephropathy.
Focal segmental glomerulosclerosis 1
MedGen UID:
4904
Concept ID:
C0017668
Disease or Syndrome
Focal segmental glomerulosclerosis (FSGS) is a pathologic finding in several renal disorders that manifest clinically as proteinuria and progressive decline in renal function. Some patients with FSGS develop the clinical entity called 'nephrotic syndrome' (see NPHS1; 256300), which includes massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. However, patients with FSGS may have proteinuria in the nephrotic range without other features of the nephrotic syndrome (summary by D'Agati et al., 2004; Mathis et al., 1998). D'Agati et al. (2011) provided a detailed review of FSGS, emphasizing that the disorder results from defects of the podocyte. Because of confusion in the literature regarding use of the terms 'nephrotic syndrome' and 'focal segmental glomerulosclerosis' (see NOMENCLATURE section), these disorders in OMIM are classified as NPHS or FSGS according to how they were first designated in the literature. Genetic Heterogeneity of Focal Segmental Glomerulosclerosis and Nephrotic Syndrome Focal segmental glomerulosclerosis and nephrotic syndrome are genetically heterogeneous disorders representing a spectrum of hereditary renal diseases. See also FSGS2 (603965), caused by mutation in the TRPC6 gene (603652); FSGS3 (607832), associated with variation in the CD2AP gene (604241); FSGS4 (612551), mapped to chromosome 22q12; FSGS5 (613237), caused by mutation in the INF2 gene (610982); FSGS6 (614131), caused by mutation in the MYO1E gene (601479); FSGS7 (616002), caused by mutation in the PAX2 gene (167409); FSGS8 (616032), caused by mutation in the ANLN gene (616027); and FSGS9 (616220), caused by mutation in the CRB2 gene (609720). See also NPHS1 (256300), caused by mutation in the NPHS1 gene (602716); NPHS2 (600995), caused by mutation in the podocin gene (604766); NPHS3 (610725), caused by mutation in the PLCE1 gene (608414); and NPHS4 (256370), caused by mutation in the WT1 gene (607102).
Glycogen storage disease, type I
MedGen UID:
6640
Concept ID:
C0017920
Disease or Syndrome
Glycogen storage disease type I (GSDI) is characterized by accumulation of glycogen and fat in the liver and kidneys, resulting in hepatomegaly and renomegaly. The two subtypes (GSDIa and GSDIb) are clinically indistinguishable. Although some untreated neonates present with severe hypoglycemia, more commonly, untreated infants present at age three to four months with hepatomegaly, lactic acidosis, hyperuricemia, hyperlipidemia, hypertriglyceridemia and/or hypoglycemic seizures. Affected children typically have doll-like faces with fat cheeks, relatively thin extremities, short stature, and protuberant abdomen. Xanthoma and diarrhea may be present. Impaired platelet function can lead to a bleeding tendency with frequent epistaxis. Untreated GSDIb is associated with impaired neutrophil and monocyte function as well as chronic neutropenia after the first few years of life, all of which result in recurrent bacterial infections and oral and intestinal mucosal ulcers. Long-term complications of untreated GSDI include growth retardation resulting in short stature, osteoporosis, delayed puberty, gout, renal disease, pulmonary hypertension, hepatic adenomas with potential for malignant transformation, polycystic ovaries, pancreatitis, and changes in brain function. Normal growth and puberty may be expected in treated children. Many affected individuals live into adulthood.
Wilson's disease
MedGen UID:
42426
Concept ID:
C0019202
Disease or Syndrome
Wilson disease is a disorder of copper metabolism that can present with hepatic, neurologic, or psychiatric disturbances, or a combination of these, in individuals ranging from age three years to over 50 years; symptoms vary among and within families. Liver disease includes recurrent jaundice, simple acute self-limited hepatitis-like illness, autoimmune-type hepatitis, fulminant hepatic failure, or chronic liver disease. Neurologic presentations include movement disorders (tremors, poor coordination, loss of fine-motor control, chorea, choreoathetosis) or rigid dystonia (mask-like facies, rigidity, gait disturbance, pseudobulbar involvement). Psychiatric disturbance includes depression, neurotic behaviors, disorganization of personality, and, occasionally, intellectual deterioration. Kayser-Fleischer rings, frequently present, result from copper deposition in Descemet's membrane of the cornea and reflect a high degree of copper storage in the body.
Norum disease
MedGen UID:
9698
Concept ID:
C0023195
Disease or Syndrome
Lecithin:cholesterol acyltransferase deficiency is a disorder of lipoprotein metabolism and causes a typical triad of diffuse corneal opacities, target cell hemolytic anemia, and proteinuria with renal failure.
Acute febrile mucocutaneous lymph node syndrome
MedGen UID:
10118
Concept ID:
C0026691
Disease or Syndrome
Kawasaki disease is an acute, self-limited vasculitis of infants and children characterized by prolonged fever unresponsive to antibiotics, polymorphous skin rash, erythema of the oral mucosa, lips, and tongue, erythema of the palms and soles, bilateral conjunctival injection, and cervical lymphadenopathy (Kawasaki, 1967). Coronary artery aneurysms develop in 15 to 25% of those left untreated (Kato et al., 1975, 1996), making Kawasaki disease the leading cause of acquired heart disease among children in developed countries. Treatment with intravenous immunoglobulin (IVIG) abrogates the inflammation in approximately 80% of affected individuals and reduces the aneurysm rate to less than 5%. Cardiac sequelae of the aneurysms include ischemic heart disease, myocardial infarction, and sudden death. Epidemiologic features such as seasonality and clustering of cases suggested an infectious trigger, although no pathogen had been isolated. Several lines of evidence suggested the importance of genetic factors in disease susceptibility and outcome. First, the incidence of Kawasaki disease is 10 to 20 times higher in Japan than in Western countries (Cook et al., 1989). Second, the risk of Kawasaki disease in sibs of affected children is 10 times higher than in the general population, and the incidence of Kawasaki disease in children born to parents with a history of Kawasaki disease is twice as high as that in the general population (Fujita et al., 1989; Uehara et al., 2003). Hata and Onouchi (2009) reviewed current knowledge on Kawasaki disease, including epidemiology, genomewide linkage analysis, and molecular genetics.
Nail-patella syndrome
MedGen UID:
10257
Concept ID:
C0027341
Congenital Abnormality
Nail-patella syndrome (NPS) involves a classic clinical tetrad of changes in the nails, knees, and elbows, and the presence of iliac horns. Nail changes are the most constant feature of NPS. Nails may be absent, hypoplastic, or dystrophic; ridged longitudinally or horizontally; pitted; discolored; separated into two halves by a longitudinal cleft or ridge of skin; and thin or (less often) thickened. The patellae may be small, irregularly shaped, or absent. Elbow abnormalities may include limitation of extension, pronation, and supination; cubitus valgus; and antecubital pterygia. Iliac horns are bilateral, conical, bony processes that project posteriorly and laterally from the central part of the iliac bones of the pelvis. Renal involvement, first manifest as proteinuria with or without hematuria, occurs in 30%-50% of affected individuals; end-stage renal disease (ESRD) occurs in about 5% of affected individuals. Primary open-angle glaucoma and ocular hypertension occur at increased frequency and at a younger age than in the general population.
Lowe syndrome
MedGen UID:
18145
Concept ID:
C0028860
Disease or Syndrome
Lowe syndrome (oculocerebrorenal syndrome) is characterized by involvement of the eyes, central nervous system, and kidneys. Dense congenital cataracts are found in all affected boys and infantile glaucoma in approximately 50%. All boys have impaired vision; corrected acuity is rarely better than 20/100. Generalized hypotonia is noted at birth and is of central (brain) origin. Deep tendon reflexes are usually absent. Hypotonia may slowly improve with age, but normal motor tone and strength are never achieved. Motor milestones are delayed. Almost all affected males have some degree of intellectual disability; 10%-25% function in the low-normal or borderline range, approximately 25% in the mild-to-moderate range, and 50%-65% in the severe-to-profound range of intellectual disability. Affected males have varying degrees of proximal renal tubular dysfunction of the Fanconi type, including bicarbonate wasting and renal tubular acidosis, phosphaturia with hypophosphatemia and renal rickets, aminoaciduria, low molecular-weight (LMW) proteinuria, sodium and potassium wasting, and polyuria. Fanconi syndrome is usually not clinically apparent in the first few months of life, but symptoms may appear by age six to 12 months. Glomerulosclerosis associated with chronic tubular injury usually results in slowly progressive chronic renal failure and end-stage renal disease after age ten to 20 years.
Pheochromocytoma
MedGen UID:
18419
Concept ID:
C0031511
Neoplastic Process
Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes are characterized by paragangliomas (tumors that arise from neuroendocrine tissues symmetrically distributed along the paravertebral axis from the base of the skull to the pelvis) and by pheochromocytomas (paragangliomas that are confined to the adrenal medulla). Sympathetic paragangliomas hypersecrete catecholamines; parasympathetic paragangliomas are most often nonsecretory. Extra-adrenal parasympathetic paragangliomas are located predominantly in the skull base, neck, and upper medistinum; approximately 95% of such tumors are nonsecretory. In contrast, sympathetic extra-adrenal paragangliomas are generally confined to the lower mediastinum, abdomen, and pelvis, and are typically secretory. Pheochromocytomas, which arise from the adrenal medulla, typically hypersecrete catecholamines. Symptoms of PGL/PCC result either from mass effects or catecholamine hypersecretion (e.g., sustained or paroxysmal elevations in blood pressure, headache, episodic profuse sweating, forceful palpitations, pallor, and apprehension or anxiety). The risk for malignant transformation is greater for extra-adrenal sympathetic paragangliomas than for pheochromocytomas or skull base and neck paragangliomas.
Preeclampsia/eclampsia 1
MedGen UID:
18608
Concept ID:
C0032914
Pathologic Function
Preeclampsia, which along with chronic hypertension and gestational hypertension comprise the hypertensive disorders of pregnancy, is characterized by new hypertension (blood pressure 140/90 or greater) presenting after 20 weeks' gestation with clinically relevant proteinuria. Preeclampsia is 1 of the top 4 causes of maternal mortality and morbidity worldwide (summary by Payne et al., 2011). Preeclampsia is otherwise known as gestational proteinuric hypertension (Davey and MacGillivray, 1988). A high proportion of patients with preeclampsia have glomerular endotheliosis, the unique histopathologic feature of the condition (Fisher et al., 1981). A distinct form of severe preeclampsia is characterized by hemolysis, elevated liver enzymes, and low platlets (HELLP syndrome) (Brown et al., 2000). Genetic Heterogeneity of Preeclampsia/Eclampsia Susceptibility loci for preeclampsia/eclampsia include PEE1 on chromosome 2p13, PEE2 (609402) on chromosome 2p25, and PEE3 (609403) on chromosome 9p13. PEE4 (609404) is caused by mutation in the STOX1 gene (609397) on chromosome 10q22. PEE5 (614595) is caused by mutation in the CORIN gene (605236) on chromosome 4p12. An association with PEE has been found with the EPHX1 gene (132810) on chromosome 1q.
Classic Kaposi sarcoma
MedGen UID:
11321
Concept ID:
C0036220
Neoplastic Process
Kaposi sarcoma (KS) is an invasive angioproliferative inflammatory condition that occurs commonly in men infected with human immunodeficiency virus (HIV; see 609423). In the early stages of KS, lesions appear reactive and are stimulated to grow by the actions of inflammatory cytokines and growth factors. In the late stages of KS, a malignant phenotype that appears to be monoclonal can develop. Infection with human herpesvirus-8 (HHV-8), also known as KS-associated herpesvirus (KSHV), is necessary but not sufficient for KS development. Coinfection with HIV markedly increases the likelihood of KS development, and additional environmental, hormonal, and genetic cofactors likely contribute to its pathogenesis (summary by Foster et al., 2000). Suthaus et al. (2012) noted that HHV-8 is the etiologic agent not only of KS, but also of primary effusion lymphoma and plasma cell-type multicentric Castleman disease (MCD).
Wegener's granulomatosis
MedGen UID:
12144
Concept ID:
C0043092
Disease or Syndrome
Wegener granulomatosis (WG) is a systemic disease with a complex genetic background. It is characterized by necrotizing granulomatous inflammation of the upper and lower respiratory tract, glomerulonephritis, vasculitis, and the presence of antineutrophil cytoplasmatic autoantibodies (ANCAs) in patient sera. These ANCAs are antibodies to a defined target antigen, proteinase-3 (PR3, PRTN3; 177020), that is present within primary azurophil granules of neutrophils (PMNs) and lysozymes of monocytes. On cytokine priming of PMNs, PR3 translocates to the cell surface, where PR3-ANCAs can interact with their antigens and activate PMNs. PMNs from patients with active WG express PR3 on their surface, produce respiratory burst, and release proteolytic enzymes after activation with PR3-ANCAs. The consequence is a self-sustaining inflammatory process (Jagiello et al., 2004).
Acute febrile neutrophilic dermatosis
MedGen UID:
43097
Concept ID:
C0085077
Disease or Syndrome
A rare syndrome characterized by fever, skin papules and plaques, and leukocytosis. Morphologically, the skin lesions show neutrophilic infiltrates and dermal edema. It may occur in the absence of underlying conditions. It may also be associated with the presence of cancer or may be a side effect of medications.
Juvenile myopathy, encephalopathy, lactic acidosis AND stroke
MedGen UID:
56485
Concept ID:
C0162671
Disease or Syndrome
MELAS syndrome, comprising mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with a variable clinical phenotype. The disorder is accompanied by features of central nervous system involvement, including seizures, hemiparesis, hemianopsia, cortical blindness, and episodic vomiting (Pavlakis et al., 1984; Montagna et al., 1988). Other mitochondrial encephalomyopathies include Leigh syndrome (LS; 256000), Kearns-Sayre syndrome (KSS; 530000), MERRF syndrome (545000), and Leber optic atrophy (535000).
Williams syndrome
MedGen UID:
59799
Concept ID:
C0175702
Disease or Syndrome
Williams syndrome (WS) is characterized by cardiovascular disease (elastin arteriopathy, peripheral pulmonary stenosis, supravalvar aortic stenosis, hypertension), distinctive facies, connective tissue abnormalities, intellectual disability (usually mild), a specific cognitive profile, unique personality characteristics, growth abnormalities, and endocrine abnormalities (hypercalcemia, hypercalciuria, hypothyroidism, and early puberty). Feeding difficulties often lead to failure to thrive in infancy. Hypotonia and hyperextensible joints can result in delayed attainment of motor milestones.
Acquired partial lipodystrophy
MedGen UID:
66352
Concept ID:
C0220989
Disease or Syndrome
Acquired partial lipodystrophy is characterized clinically by the gradual onset of bilaterally symmetrical loss of subcutaneous fat from the face, neck, upper extremities, thorax, and abdomen, in the 'cephalocaudal' sequence, sparing the lower extremities (summary by Misra et al., 2004). The disorder is not inherited in a classic mendelian pattern; it rather represents a phenotype with a complex etiology. Affected individuals may have genetic susceptibility factors that require the additional presence of environmental factors or acquired disorders to be expressed (summary by Hegele et al., 2006). Most cases are sporadic, family history is negative, and females are more often affected than males (ratio, 4:1). There is an association between APLD and autoimmune diseases (Misra and Garg, 2003; Misra et al., 2004), and a subset of patients have APLD associated with low serum complement component C3 and the autoantibody C3 nephritic factor, with or without membranoproliferative glomerulonephritis (APLDC3; 613913). Acquired partial lipodystrophy is distinct from inherited forms of partial lipodystrophy, which are metabolic disorders that show clear mendelian inheritance (see, e.g., FPLD1, 608600).
Jeune thoracic dystrophy
MedGen UID:
78548
Concept ID:
C0265275
Congenital Abnormality
Asphyxiating thoracic dystrophy, also known as Jeune syndrome, is an inherited disorder of bone growth characterized by a small chest, short ribs, and shortened bones in the arms and legs. Additional skeletal abnormalities can include unusually shaped pelvic bones and extra fingers and/or toes (polydactyly). Infants with this condition are born with an extremely narrow, bell-shaped chest that can restrict the growth and expansion of the lungs. Life-threatening problems with breathing often result, and most people with asphyxiating thoracic dystrophy live only into infancy or early childhood. Some people with asphyxiating thoracic dystrophy experience only mild breathing difficulties, such as rapid breathing or shortness of breath. These individuals may live into adolescence or adulthood. After infancy, people with this condition often develop life-threatening kidney (renal) abnormalities that cause the kidneys to malfunction or fail. Heart defects and a narrowing of the airway (subglottic stenosis) are also possible. Other, less common features of asphyxiating thoracic dystrophy include liver disease, pancreatic cysts, dental abnormalities, and an eye disease called retinal dystrophy that can lead to vision loss.
Distichiasis-lymphedema syndrome
MedGen UID:
75566
Concept ID:
C0265345
Congenital Abnormality
Lymphedema-distichiasis syndrome is characterized by lower-limb lymphedema and distichiasis (aberrant eyelashes ranging from a full set of extra eyelashes to a single hair). Lymphedema typically appears in late childhood or puberty, is confined to the lower limbs, and is often asymmetric; severity varies within families. Males develop edema at an earlier age and have more problems with cellulitis than females. Distichiasis, which may be present at birth, is observed in 94% of affected individuals. About 75% of affected individuals have ocular findings including corneal irritation, recurrent conjunctivitis, and photophobia; other common findings include varicose veins, congenital heart disease, and ptosis. About 25% of individuals are asymptomatic.
Glucose-6-phosphate transport defect
MedGen UID:
78644
Concept ID:
C0268146
Congenital Abnormality
Glycogen storage disease type I (GSDI) is characterized by accumulation of glycogen and fat in the liver and kidneys, resulting in hepatomegaly and renomegaly. The two subtypes (GSDIa and GSDIb) are clinically indistinguishable. Although some untreated neonates present with severe hypoglycemia, more commonly, untreated infants present at age three to four months with hepatomegaly, lactic acidosis, hyperuricemia, hyperlipidemia, hypertriglyceridemia and/or hypoglycemic seizures. Affected children typically have doll-like faces with fat cheeks, relatively thin extremities, short stature, and protuberant abdomen. Xanthoma and diarrhea may be present. Impaired platelet function can lead to a bleeding tendency with frequent epistaxis. Untreated GSDIb is associated with impaired neutrophil and monocyte function as well as chronic neutropenia after the first few years of life, all of which result in recurrent bacterial infections and oral and intestinal mucosal ulcers. Long-term complications of untreated GSDI include growth retardation resulting in short stature, osteoporosis, delayed puberty, gout, renal disease, pulmonary hypertension, hepatic adenomas with potential for malignant transformation, polycystic ovaries, pancreatitis, and changes in brain function. Normal growth and puberty may be expected in treated children. Many affected individuals live into adulthood.
Sialidosis, type II
MedGen UID:
120621
Concept ID:
C0268226
Disease or Syndrome
Sialidosis is an autosomal recessive disorder characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides caused by a deficiency of the enzyme neuraminidase. Common to the sialidoses is the accumulation and/or excretion of sialic acid (N-acetylneuraminic acid) covalently linked ('bound') to a variety of oligosaccharides and/or glycoproteins (summary by Lowden and O'Brien, 1979). The sialidoses are distinct from the sialurias in which there is storage and excretion of 'free' sialic acid, rather than 'bound' sialic acid; neuraminidase activity in sialuria is normal or elevated. Salla disease (604369) is a form of 'free' sialic acid disease. Classification Lowden and O'Brien (1979) provided a logical nosology of neuraminidase deficiency into sialidosis type I and type II. Type I is the milder form, also known as the 'normosomatic' type or the cherry red spot-myoclonus syndrome. Sialidosis type II is the more severe form with an earlier onset, and is also known as the 'dysmorphic' type. Type II has been subdivided into juvenile and infantile forms. Other terms for sialidosis type II are mucolipidosis I and lipomucopolysaccharidosis.
Cytochrome-c oxidase deficiency
MedGen UID:
75662
Concept ID:
C0268237
Congenital Abnormality
Complex IV (cytochrome c oxidase; EC 1.9.3.1) is the terminal enzyme of the respiratory chain and consists of 13 polypeptide subunits, 3 of which are encoded by mitochondrial DNA. The 3 mitochondrially encoded proteins in the cytochrome oxidase complex are the actual catalytic subunits that carry out the electron transport function (Saraste, 1983). See 123995 for discussion of some of the nuclear-encoded subunits. Shoubridge (2001) provided a comprehensive review of cytochrome c oxidase deficiency and noted that most isolated COX deficiencies are inherited as autosomal recessive disorders caused by mutations in nuclear-encoded genes; mutations in the mtDNA-encoded COX subunit genes are relatively rare.
Subacute neuronopathic Gaucher's disease
MedGen UID:
78653
Concept ID:
C0268251
Disease or Syndrome
Gaucher disease (GD) encompasses a continuum of clinical findings from a perinatal lethal disorder to an asymptomatic type. The identification of three major clinical types (1, 2, and 3) and two other subtypes (perinatal-lethal and cardiovascular) is useful in determining prognosis and management. GD type 1 is characterized by the presence of clinical or radiographic evidence of bone disease (osteopenia, focal lytic or sclerotic lesions, and osteonecrosis), hepatosplenomegaly, anemia and thrombocytopenia, lung disease, and the absence of primary central nervous system disease. GD types 2 and 3 are characterized by the presence of primary neurologic disease; in the past, they were distinguished by age of onset and rate of disease progression, but these distinctions are not absolute. Disease with onset before age two years, limited psychomotor development, and a rapidly progressive course with death by age two to four years is classified as GD type 2. Individuals with GD type 3 may have onset before age two years, but often have a more slowly progressive course, with survival into the third or fourth decade. The perinatal-lethal form is associated with ichthyosiform or collodion skin abnormalities or with nonimmune hydrops fetalis. The cardiovascular form is characterized by calcification of the aortic and mitral valves, mild splenomegaly, corneal opacities, and supranuclear ophthalmoplegia. Cardiopulmonary complications have been described with all the clinical subtypes, although varying in frequency and severity.
Familial visceral amyloidosis, Ostertag type
MedGen UID:
82799
Concept ID:
C0268389
Congenital Abnormality
Luder-Sheldon Syndrome
MedGen UID:
75680
Concept ID:
C0268440
Disease or Syndrome
Proline dehydrogenase deficiency
MedGen UID:
120645
Concept ID:
C0268529
Disease or Syndrome
Phang et al. (2001) noted that prospective studies of HPI probands identified through newborn screening as well as reports of several families have suggested that it is a metabolic disorder not clearly associated with clinical manifestations. Phang et al. (2001) concluded that HPI is a relatively benign condition in most individuals under most circumstances. However, other reports have suggested that some patients have a severe phenotype with neurologic manifestations, including epilepsy and mental retardation (Jacquet et al., 2003). Genetic Heterogeneity of Hyperprolinemia See also hyperprolinemia type II (HYRPRO2; 239510), which is caused by mutation in the gene encoding pyrroline-5-carboxylate dehydrogenase (P5CDH, ALDH4A1; 606811) on chromosome 1p36.
Juvenile nephropathic cystinosis
MedGen UID:
75701
Concept ID:
C0268626
Congenital Abnormality
Nephropathic cystinosis in untreated children is characterized by renal tubular Fanconi syndrome, poor growth, hypophosphatemic rickets, impaired glomerular function resulting in complete glomerular failure, and accumulation of cystine crystals in almost all cells, leading to cellular destruction and tissue dysfunction. The typical untreated child has short stature, light complexion, rickets, and photophobia. Failure to thrive is generally noticed after approximately age six months; signs of renal tubular Fanconi syndrome (polyuria, polydipsia, dehydration, and acidosis) appear as early as age six months; corneal crystals can be present before age one year and are always present after age 16 months. Prior to the use of renal transplantation and cystine-depleting therapy, the life span in nephropathic cystinosis was no longer than ten years. With these therapies, affected individuals can survive at least into the mid-forties or fifties with satisfactory quality of life. Intermediate cystinosis is characterized by all the typical manifestations of nephropathic cystinosis, but onset is at a later age. Renal glomerular failure occurs in all untreated affected individuals, usually between ages 15 and 25 years. The non-nephropathic (ocular) form of cystinosis is characterized only by photophobia resulting from corneal cystine crystal accumulation.
De Lange syndrome
MedGen UID:
78752
Concept ID:
C0270972
Congenital Abnormality
Classic Cornelia de Lange syndrome (CdLS) is characterized by distinctive facial features, growth retardation (prenatal onset; <5th centile throughout life), hirsutism, and upper limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly (missing digits). Craniofacial features include synophrys, arched eyebrows, long eyelashes, small upturned nose, small widely spaced teeth, and microcephaly. IQ ranges from below 30 to 102 (mean: 53). Many individuals demonstrate autistic and self-destructive tendencies. Frequent findings include cardiac septal defects, gastrointestinal dysfunction, hearing loss, myopia, and cryptorchidism or hypoplastic genitalia. Individuals with a milder phenotype have less severe growth, cognitive, and limb involvement, but often have facial features consistent with CdLS.
Pineal hyperplasia AND diabetes mellitus syndrome
MedGen UID:
78783
Concept ID:
C0271695
Disease or Syndrome
Rabson-Mendenhall syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. In people with Rabson-Mendenhall syndrome, insulin resistance impairs blood sugar regulation and ultimately leads to a condition called diabetes mellitus, in which blood sugar levels can become dangerously high. Severe insulin resistance in people with Rabson-Mendenhall syndrome affects the development of many parts of the body. Affected individuals are unusually small starting before birth, and infants experience failure to thrive, which means they do not grow and gain weight at the expected rate. Additional features of the condition that become apparent early in life include a lack of fatty tissue under the skin (subcutaneous fat); wasting (atrophy) of muscles; dental abnormalities; excessive body hair growth (hirsutism); multiple cysts on the ovaries in females; and enlargement of the nipples, genitalia, kidneys, heart, and other organs. Most affected individuals also have a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Distinctive facial features in people with Rabson-Mendenhall syndrome include prominent, widely spaced eyes; a broad nose; and large, low-set ears. Rabson-Mendenhall syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Donohue syndrome and type A insulin resistance syndrome, are considered part of a spectrum. Rabson-Mendenhall syndrome is intermediate in severity between Donohue syndrome (which is fatal before age 2) and type A insulin resistance syndrome (which is often not diagnosed until adolescence). People with Rabson-Mendenhall syndrome develop signs and symptoms early in life and live into their teens or twenties. Death usually results from complications related to diabetes mellitus, such as a toxic buildup of acids called ketones in the body (diabetic ketoacidosis).
Adult Fanconi syndrome
MedGen UID:
137960
Concept ID:
C0341703
Disease or Syndrome
Probably related to a recessive gene, this is Fanconi Syndrome, characterised by adult onset. -- 2003
Diabetes-deafness syndrome maternally transmitted
MedGen UID:
90979
Concept ID:
C0342289
Congenital Abnormality
Maternally inherited diabetes-deafness syndrome (MIDD) is a mitochondrial disorder characterized by onset of sensorineural hearing loss and diabetes in adulthood. Some patients may have additional features observed in mitochondrial disorders, including pigmentary retinopathy, ptosis, cardiomyopathy, myopathy, renal problems, and neuropsychiatric symptoms (Ballinger et al., 1992; Reardon et al., 1992; Guillausseau et al., 2001). The association of diabetes and deafness is observed with Wolfram syndrome (see 222300), Rogers syndrome (249270), and Herrmann syndrome (172500), but all 3 of these disorders have other clinical manifestations.
Phosphate transport defect
MedGen UID:
87455
Concept ID:
C0342749
Disease or Syndrome
Carbohydrate-deficient glycoprotein syndrome type I
MedGen UID:
138111
Concept ID:
C0349653
Disease or Syndrome
PMM2-CDG (CDG-Ia) (previously known as congenital disorder of glycosylation type 1a), the most common of a group of disorders of abnormal glycosylation of N-linked oligosaccharides, is divided into three stages: infantile multisystem, late-infantile and childhood ataxia-intellectual disability, and adult stable disability. The three stages notwithstanding, clinical presentation and course are highly variable, ranging from infants who die in the first year of life to mildly involved adults. Clinical presentations tend to be similar in siblings. In the infantile multisystem stage, infants show axial hypotonia, hyporeflexia, esotropia, and developmental delay; feeding problems, vomiting, and diarrhea with failure to thrive; and impaired growth. Subcutaneous fat may be excessive over the buttocks and suprapubic region. Two distinct clinical presentations are observed: (1) a non-fatal neurologic form with strabismus, psychomotor retardation, and cerebellar hypoplasia in infancy followed by neuropathy and retinitis pigmentosa in the first or second decade and (2) a neurologic-multivisceral form with approximately 20% mortality in the first year of life. The late-infantile and childhood ataxia-intellectual disability stage, with onset between age three and ten years, is characterized by hypotonia, ataxia, severely delayed language and motor development, inability to walk, and IQ of 40 to 70; other findings include stroke-like episodes or transient unilateral loss of function, retinitis pigmentosa, joint contractures, and skeletal deformities. In the adult stable disability stage, intellectual ability is stable; peripheral neuropathy is variable, thoracic and spinal deformities progress, and premature aging is observed; females lack secondary sexual development and males may exhibit decreased testicular volume. Hyperglycemia-induced growth hormone release, hyperprolactinemia, insulin resistance, and coagulopathy may occur. An increased risk of deep venous thrombosis is present.
Epstein syndrome
MedGen UID:
97986
Concept ID:
C0398641
Disease or Syndrome
MYH9-related disorders (MYH9RD) are characterized by large platelets (i.e., >20% of platelets >4 µm in diameter) and thrombocytopenia (platelet count <150x10(9)/L), both of which are present from birth. MYH9RD is variably associated with young-adult onset of progressive high-frequency sensorineural hearing loss, presenile cataract, and renal disease manifesting initially as glomerulonephritis. Before identification of the gene in which mutation is causative, MYH9, individuals with MYH9RD were diagnosed as having Epstein syndrome, Fechtner syndrome, May-Hegglin anomaly, or Sebastian syndrome based on the combination of different clinical findings at the time of diagnosis. However, the realization that they all have MYH9 mutations and that their clinical picture often worsens throughout life as a result of late onset of non-hematologic manifestations has led the four conditions to be regarded as one disorder, now known as MYH9RD.
Biliary malformation associated with renal tubular insufficiency
MedGen UID:
98009
Concept ID:
C0400972
Congenital Abnormality
Finnish congenital nephrotic syndrome
MedGen UID:
98011
Concept ID:
C0403399
Disease or Syndrome
The nephrotic syndrome is characterized clinically by proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Kidney biopsies show nonspecific histologic changes such as minimal change, focal segmental glomerulosclerosis (FSGS), and diffuse mesangial proliferation. Approximately 20% of affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure (summary by Fuchshuber et al., 1996). Nephrotic syndrome type 1 (NPHS1) is characterized by prenatal onset of massive proteinuria followed by severe steroid-resistant nephrotic syndrome apparent at birth with rapid progression to end-stage renal failure (Kestila et al., 1998). Because of confusion in the literature regarding use of the terms 'nephrotic syndrome' and 'focal segmental glomerulosclerosis' (see NOMENCLATURE section), these disorders in OMIM are classified as NPHS or FSGS according to how they were first designated in the literature. Genetic Heterogeneity of Nephrotic Syndrome and Focal Segmental Glomerulosclerosis Nephrotic syndrome and FSGS are genetically heterogeneous disorders representing a spectrum of hereditary renal diseases. See also NPHS2 (600995), caused by mutation in the podocin gene (604766); NPHS3 (610725), caused by mutation in the PLCE1 gene (608414); NPHS4 (256370), caused by mutation in the WT1 gene (607102); NPHS5 (614199), caused by mutation in the LAMB2 gene (150325); NPHS6 (614196), caused by mutation in the PTPRO gene (600579); NPHS7 (615008), caused by mutation in the DGKE gene (601440); NPHS8 (615244), caused by mutation in the ARHGDIA gene (601925); NPHS9 (615573), caused by mutation in the ADCK4 gene (615567); and NPHS10 (615861), caused by mutation in the EMP2 gene (602334). FSGS1 (603278) is caused by mutation in the ACTN4 gene (604638) and FSGS2 (603965) by mutation in the TRPC6 gene (603652). FSGS3 (607832) is associated with variation in the CD2AP gene (604241). FSGS4 (612551) has been mapped to chromosome 22q12, and FSGS5 (613237) is caused by mutation in the INF2 gene (610982).
Progressive hereditary glomerulonephritis without deafness
MedGen UID:
98012
Concept ID:
C0403443
Disease or Syndrome
Fechtner syndrome
MedGen UID:
96041
Concept ID:
C0403445
Disease or Syndrome
MYH9-related disorders (MYH9RD) are characterized by large platelets (i.e., >20% of platelets >4 µm in diameter) and thrombocytopenia (platelet count <150x10(9)/L), both of which are present from birth. MYH9RD is variably associated with young-adult onset of progressive high-frequency sensorineural hearing loss, presenile cataract, and renal disease manifesting initially as glomerulonephritis. Before identification of the gene in which mutation is causative, MYH9, individuals with MYH9RD were diagnosed as having Epstein syndrome, Fechtner syndrome, May-Hegglin anomaly, or Sebastian syndrome based on the combination of different clinical findings at the time of diagnosis. However, the realization that they all have MYH9 mutations and that their clinical picture often worsens throughout life as a result of late onset of non-hematologic manifestations has led the four conditions to be regarded as one disorder, now known as MYH9RD.
Goodpasture syndrome
MedGen UID:
140788
Concept ID:
C0403529
Disease or Syndrome
An autoimmune disorder characterized by the production of autoantibodies against type IV collagen of the glomerular basement membrane of the kidney. In the majority of patients the immune reaction also extends to the alveolar capillary membrane of the lungs. The latter cases are referred to as Goodpasture Syndrome.
Nail patella-like renal disease
MedGen UID:
140789
Concept ID:
C0403548
Disease or Syndrome
Glomerulopathy with giant fibrillar deposits
MedGen UID:
98017
Concept ID:
C0403557
Disease or Syndrome
Glomerulopathy with fibronectin deposits (GFND) is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life. Pathologic examination shows enlarged glomeruli with mesangial and subendothelial fibrillary deposits that show strong immunoreactivity to fibronectin (FN1; 135600) (Castelletti et al., 2008). Genetic Heterogeneity of Glomerulopathy with Fibronectin Deposits The GFND1 locus maps to chromosome 1q32. See also GFND2 (601894), which is caused by mutation in the FN1 gene (135600) on chromosome 2q34.
Familial hypoplastic, glomerulocystic kidney
MedGen UID:
96569
Concept ID:
C0431693
Congenital Abnormality
The 'renal cysts and diabetes syndrome' is an autosomal dominant disorder comprising (1) nondiabetic renal disease resulting from abnormal renal development, and (2) diabetes, which in some cases occurs earlier than age 25 years and is thus consistent with a diagnosis of maturity-onset diabetes of the young (MODY). The renal disease is highly variable and includes renal cysts, glomerular tufts, aberrant nephrogenesis, primitive tubules, irregular collecting systems, oligomeganephronia, enlarged renal pelvises, abnormal calyces, small kidney, single kidney, horseshoe kidney, and hyperuricemic nephropathy. Affected individuals may also have abnormalities of the genital tract, including vaginal aplasia, rudimentary uterus, bicornuate uterus, epididymal cysts, and atresia of the vas deferens (Bingham et al., 2001; Fajans et al., 2001; Bellanne-Chantelot et al., 2004; Edghill et al., 2006). The renal abnormalities seen in the RCAD syndrome are part of a spectrum of malformations known as congenital anomalies of the kidney and urinary tract (CAKUT; see 610805) (summary by Nakayama et al., 2010).
Cockayne syndrome type C
MedGen UID:
196713
Concept ID:
C0751037
Disease or Syndrome
Cockayne syndrome is a rare disorder characterized by short stature and an appearance of premature aging. Features of this disorder include a failure to gain weight and grow at the expected rate (failure to thrive), abnormally small head size (microcephaly), and impaired development of the nervous system. Affected individuals have an extreme sensitivity to sunlight (photosensitivity), and even a small amount of sun exposure can cause a sunburn. Other possible signs and symptoms include hearing loss, eye abnormalities, severe tooth decay, bone abnormalities, and changes in the brain that can be seen on brain scans. Cockayne syndrome can be divided into subtypes, which are distinguished by the severity and age of onset of symptoms. Classical, or type I, Cockayne syndrome is characterized by an onset of symptoms in early childhood (usually after age 1 year). Type II Cockayne syndrome has much more severe symptoms that are apparent at birth (congenital). Type II Cockayne syndrome is sometimes called cerebro-oculo-facio-skeletal (COFS) syndrome or Pena-Shokeir syndrome type II. Type III Cockayne syndrome has the mildest symptoms of the three types and appears later in childhood.
Cockayne syndrome, type B
MedGen UID:
155487
Concept ID:
C0751038
Disease or Syndrome
Cockayne syndrome (referred to as CS in this GeneReview) spans a phenotypic spectrum that includes: CS type I, the "classic" or “moderate” form; CS type II, a more severe form with symptoms present at birth; this form overlaps with cerebrooculofacioskeletal syndrome (COFS) or Pena-Shokeir syndrome type II; CS type III, a milder form; Xeroderma pigmentosum-Cockayne syndrome (XP-CS). CS type I (moderate CS) is characterized by normal prenatal growth with the onset of growth and developmental abnormalities in the first two years. By the time the disease has become fully manifest, height, weight, and head circumference are far below the fifth percentile. Progressive impairment of vision, hearing, and central and peripheral nervous system function leads to severe disability; death typically occurs in the first or second decade. CS type II (severe CS or early-onset CS) is characterized by growth failure at birth, with little or no postnatal neurologic development. Congenital cataracts or other structural anomalies of the eye may be present. Affected children have early postnatal contractures of the spine (kyphosis, scoliosis) and joints. Death usually occurs by age seven years. CS type III (mild CS or late-onset CS) is characterized by essentially normal growth and cognitive development or by late onset. Xeroderma pigmentosum-Cockayne syndrome (XP-CS) includes facial freckling and early skin cancers typical of XP and some features typical of CS, including intellectual disability, spasticity, short stature, and hypogonadism. XP-CS does not include skeletal involvement, the facial phenotype of CS, or CNS dysmyelination and calcifications.
Cockayne syndrome type A
MedGen UID:
155488
Concept ID:
C0751039
Disease or Syndrome
Cockayne syndrome (referred to as CS in this GeneReview) spans a phenotypic spectrum that includes: CS type I, the "classic" or “moderate” form; CS type II, a more severe form with symptoms present at birth; this form overlaps with cerebrooculofacioskeletal syndrome (COFS) or Pena-Shokeir syndrome type II; CS type III, a milder form; Xeroderma pigmentosum-Cockayne syndrome (XP-CS). CS type I (moderate CS) is characterized by normal prenatal growth with the onset of growth and developmental abnormalities in the first two years. By the time the disease has become fully manifest, height, weight, and head circumference are far below the fifth percentile. Progressive impairment of vision, hearing, and central and peripheral nervous system function leads to severe disability; death typically occurs in the first or second decade. CS type II (severe CS or early-onset CS) is characterized by growth failure at birth, with little or no postnatal neurologic development. Congenital cataracts or other structural anomalies of the eye may be present. Affected children have early postnatal contractures of the spine (kyphosis, scoliosis) and joints. Death usually occurs by age seven years. CS type III (mild CS or late-onset CS) is characterized by essentially normal growth and cognitive development or by late onset. Xeroderma pigmentosum-Cockayne syndrome (XP-CS) includes facial freckling and early skin cancers typical of XP and some features typical of CS, including intellectual disability, spasticity, short stature, and hypogonadism. XP-CS does not include skeletal involvement, the facial phenotype of CS, or CNS dysmyelination and calcifications.
Epilepsy, progressive myoclonic 4, with or without renal failure
MedGen UID:
155629
Concept ID:
C0751779
Disease or Syndrome
The action myoclonus-renal failure syndrome is an autosomal recessive progressive myoclonic epilepsy associated with renal failure. Cognitive function is preserved (Badhwar et al., 2004). Some patients do not develop renal failure (Dibbens et al., 2009). For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800).
Microcephaly, hiatal hernia and nephrotic syndrome
MedGen UID:
167086
Concept ID:
C0795949
Disease or Syndrome
Galloway-Mowat syndrome is a rare autosomal recessive disorder characterized by microcephaly and central nervous system abnormalities resulting in severe intellectual disability. Most patients also develop seizures and nephrotic syndrome later in childhood. Many affected children die in the first decade of life (summary by Colin et al., 2014).
Mental retardation, congenital heart disease, blepharophimosis, blepharoptosis and hypoplastic teeth
MedGen UID:
162905
Concept ID:
C0796094
Disease or Syndrome
A syndrome of delayed development, blepharophimosis, blepharoptosis, dental hypoplasia, deafness, heart defect, cryptorchidism and scrotal hypoplasia in males, and other abnormalities.
Schimke immunoosseous dysplasia
MedGen UID:
164078
Concept ID:
C0877024
Congenital Abnormality
Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive multisystem disorder characterized by spondyloepiphyseal dysplasia (SED) resulting in short stature, nephropathy, and T-cell deficiency. Radiographic manifestations of SED include ovoid and mildly flattened vertebral bodies, small deformed capital femoral epiphyses, and shallow dysplastic acetabular fossae. Adult height is 136-157 cm for men and 98.5-143 cm for women. Nearly all affected individuals have progressive steroid-resistant nephropathy, usually developing within five years of the diagnosis of growth failure and terminating with end-stage renal disease (ESRD). The majority of tested individuals have T-cell deficiency and associated risk for opportunistic infection, a common cause of death. SIOD involves a spectrum that ranges from an infantile or severe early-onset form with death early in life to a juvenile or milder later-onset form with survival into adulthood if renal disease is appropriately treated.
Drash syndrome
MedGen UID:
181980
Concept ID:
C0950121
Disease or Syndrome
Denys-Drash syndrome is a condition that affects the kidneys and genitalia. Denys-Drash syndrome is characterized by kidney disease that begins within the first few months of life. Affected individuals have a condition called diffuse glomerulosclerosis, in which scar tissue forms throughout glomeruli, which are the tiny blood vessels in the kidneys that filter waste from blood. In people with Denys-Drash syndrome, this condition often leads to kidney failure in childhood. People with Denys-Drash syndrome have an estimated 90 percent chance of developing a rare form of kidney cancer known as Wilms tumor. Affected individuals may develop multiple tumors in one or both kidneys. Although males with Denys-Drash syndrome have the typical male chromosome pattern (46,XY), they have gonadal dysgenesis, in which external genitalia do not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear completely female. The testes of affected males are undescended, which means they are abnormally located in the pelvis, abdomen, or groin. As a result, males with Denys-Drash are typically unable to have biological children (infertile). Affected females usually have normal genitalia and have only the kidney features of the condition. Because they do not have all the features of the condition, females are usually given the diagnosis of isolated nephrotic syndrome.
Frasier syndrome
MedGen UID:
215533
Concept ID:
C0950122
Congenital Abnormality
Frasier syndrome is a rare disorder defined by pseudohermaphroditism and progressive glomerulopathy (Frasier et al., 1964; Haning et al., 1985; Kinberg et al., 1987). Patients present with normal female external genitalia, streak gonads, and XY karyotype, and frequently develop gonadoblastoma (Blanchet et al., 1977). Glomerular symptoms consist of childhood proteinuria and nephrotic syndrome, characterized by nonspecific focal and segmental glomerular sclerosis, progressing to end-stage renal failure in adolescence or early adulthood. Wilms tumor is not a usual feature (Barbaux et al., 1997).
Upshaw-Schulman syndrome
MedGen UID:
224783
Concept ID:
C1268935
Disease or Syndrome
The classic pentad of TTP includes hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and nonfocal neurologic findings, decreased renal function, and fever. Congenital TTP, also known as Schulman-Upshaw syndrome, is characterized by neonatal onset, response to fresh plasma infusion, and frequent relapses (Savasan et al., 2003; Kokame et al., 2002). Acquired TTP, which is usually sporadic, usually occurs in adults and is caused by an IgG inhibitor against the von Willebrand factor-cleaving protease.
Megaloblastic anemia due to inborn errors of metabolism
MedGen UID:
224934
Concept ID:
C1306856
Disease or Syndrome
Type I MGCA is a rare autosomal recessive disorder of leucine catabolism. The metabolic landmark is urinary excretion of 3-methylglutaconic acid (3-MGA) and its derivatives 3-methylglutaric acid (3-MG) and 3-hydroxyisovaleric acid (3-HIVA). Two main presentations have been described: 1 with onset in childhood associated with the nonspecific finding of psychomotor retardation, and the other with onset in adulthood of a progressive neurodegenerative disorder characterized by ataxia, spasticity, and sometimes dementia; these patients develop white matter lesions in the brain. However, some asymptomatic pediatric patients have been identified by newborn screening and show no developmental abnormalities when reexamined later in childhood (summary by Wortmann et al., 2010). Genetic Heterogeneity and Classification of Methylglutaconic Aciduria Methylglutaconic aciduria is a clinically and genetically heterogeneous disorder. Type II MGCA, also known as Barth syndrome (BTHS; 302060), is caused by mutation in the tafazzin gene (TAZ; 300394) on chromosome Xq28. It is characterized by mitochondrial cardiomyopathy, short stature, skeletal myopathy, and recurrent infections; cognitive development is normal. Type III MGCA (258501), caused by mutation in the OPA3 gene (606580) on chromosome 19q13.2-q13.3, occurs in Iraqi Jews and involves optic atrophy, movement disorder, and spastic paraplegia. In types II and III, the elevations of 3-methylglutaconate and 3-methylglutarate in urine are modest. Type IV MGCA (250951) represents an unclassified group of patients who have severe psychomotor retardation and cerebellar dysgenesis. Type V MGCA (610198), caused by mutation in the DNAJC19 gene (608977) on chromosome 3q26, is characterized by early-onset dilated cardiomyopathy with conduction defects, nonprogressive cerebellar ataxia, testicular dysgenesis, and growth failure in addition to 3-methylglutaconic aciduria (Chitayat et al., 1992; Davey et al., 2006). Type VI MGCA (614739) is caused by mutation in the SERAC1 gene (614725) on chromosome 6q25. Type VII MGCA (616271) is caused by mutation in the CLPB gene (616254) on chromosome 11q13. Eriguchi et al. (2006) noted that type I MGCA is very rare, with only 13 patients reported in the literature as of 2003.
Oral-facial-digital syndrome
MedGen UID:
307142
Concept ID:
C1510460
Disease or Syndrome
Oral-facial-digital syndrome type I (OFD1) is associated with dysfunction of primary cilia and is characterized by the following abnormalities: Oral (lobed tongue, hamartomas or lipomas of the tongue, cleft of the hard or soft palate, accessory gingival frenulae, hypodontia, and other dental abnormalities). Facial (widely spaced eyes or telecanthus, hypoplasia of the alae nasi, median cleft or pseudocleft upper lip, micrognathia) . Digital (brachydactyly, syndactyly of varying degrees, and clinodactyly of the fifth finger; duplicated hallux [great toe]; preaxial or postaxial polydactyly of the hands). Brain (intracerebral cysts, corpus callosum agenesis, cerebellar agenesis with or without Dandy-Walker malformation) . Kidney (polycystic kidney disease). As many as 50% of individuals with OFD1 have some degree of intellectual disability, which is usually mild. Almost all affected individuals are female. However, males with OFD1 have been described, mostly as malformed fetuses delivered by women with OFD1.
Alport syndrome, X-linked recessive
MedGen UID:
292688
Concept ID:
C1567742
Disease or Syndrome
Alport syndrome (AS) is characterized by renal, cochlear, and ocular involvement. Renal disease progresses from microscopic hematuria to proteinuria, progressive renal insufficiency, and end-stage renal disease (ESRD) in all males with X-linked (XL) AS, and in all males and females with autosomal recessive (AR) AS. Progressive sensorineural hearing loss (SNHL) is usually present by late childhood or early adolescence. Ocular findings include anterior lenticonus (which is virtually pathognomonic), maculopathy (whitish or yellowish flecks or granulations in the perimacular region), corneal endothelial vesicles (posterior polymorphous dystrophy), and recurrent corneal erosion. Thin basement membrane nephropathy (TBMN) is characterized by persistent microscopic hematuria often first observed in childhood; progressive renal involvement and extrarenal abnormalities are rare.
Alport syndrome, autosomal dominant
MedGen UID:
339210
Concept ID:
C1567743
Disease or Syndrome
Alport syndrome (AS) is characterized by renal, cochlear, and ocular involvement. Renal disease progresses from microscopic hematuria to proteinuria, progressive renal insufficiency, and end-stage renal disease (ESRD) in all males with X-linked (XL) AS, and in all males and females with autosomal recessive (AR) AS. Progressive sensorineural hearing loss (SNHL) is usually present by late childhood or early adolescence. Ocular findings include anterior lenticonus (which is virtually pathognomonic), maculopathy (whitish or yellowish flecks or granulations in the perimacular region), corneal endothelial vesicles (posterior polymorphous dystrophy), and recurrent corneal erosion. Thin basement membrane nephropathy (TBMN) is characterized by persistent microscopic hematuria often first observed in childhood; progressive renal involvement and extrarenal abnormalities are rare.
Alport syndrome, autosomal recessive
MedGen UID:
292689
Concept ID:
C1567744
Disease or Syndrome
Alport syndrome (AS) is characterized by renal, cochlear, and ocular involvement. Renal disease progresses from microscopic hematuria to proteinuria, progressive renal insufficiency, and end-stage renal disease (ESRD) in all males with X-linked (XL) AS, and in all males and females with autosomal recessive (AR) AS. Progressive sensorineural hearing loss (SNHL) is usually present by late childhood or early adolescence. Ocular findings include anterior lenticonus (which is virtually pathognomonic), maculopathy (whitish or yellowish flecks or granulations in the perimacular region), corneal endothelial vesicles (posterior polymorphous dystrophy), and recurrent corneal erosion. Thin basement membrane nephropathy (TBMN) is characterized by persistent microscopic hematuria often first observed in childhood; progressive renal involvement and extrarenal abnormalities are rare.
Renal adysplasia
MedGen UID:
301437
Concept ID:
C1619700
Disease or Syndrome
Renal hypodysplasia/aplasia belongs to a group of perinatally lethal renal diseases, including bilateral renal aplasia, unilateral renal agenesis with contralateral dysplasia (URA/RD), and severe obstructive uropathy. Renal aplasia falls at the most severe end of the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT; 610805), and usually results in death in utero or in the perinatal period. Families have been documented in which bilateral renal agenesis or aplasia coexists with unilateral renal aplasia, renal dysplasia, or renal aplasia with renal dysplasia, suggesting that these conditions may belong to a pathogenic continuum or phenotypic spectrum (summary by Joss et al., 2003; Humbert et al., 2014). Genetic Heterogeneity of Renal Hypodysplasia/Aplasia RHDA2 (615721) is caused by mutation in the FGF20 gene (605558) on chromosome 8p22.
Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome
MedGen UID:
332113
Concept ID:
C1836033
Disease or Syndrome
CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma) syndrome refers to a unique constellation of clinical manifestations including microcephaly, severe neurologic impairment, psychomotor retardation, failure to thrive, and facial dysmorphism, as well as palmoplantar keratoderma and late-onset ichthyosis. Brain magnetic resonance imaging (MRI) shows various degrees of cerebral dysgenesis including absence of corpus callosum and cortical dysplasia. The syndrome has been found to be uniformly fatal between the ages of 5 and 12 years (Fuchs-Telem et al., 2011).
Pierson syndrome
MedGen UID:
373199
Concept ID:
C1836876
Disease or Syndrome
Pierson syndrome is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss (summary by Zenker et al., 2004). Mutations in the LAMB2 gene also cause nephrotic syndrome type 5 with or without mild ocular anomalies (NPHS5; 614199).
Torticollis keloids cryptorchidism renal dysplasia
MedGen UID:
326819
Concept ID:
C1839129
Disease or Syndrome
Leiomyomatosis, esophageal and vulval, with nephropathy
MedGen UID:
333429
Concept ID:
C1839884
Disease or Syndrome
Barakat syndrome
MedGen UID:
374443
Concept ID:
C1840333
Disease or Syndrome
Heme oxygenase 1 deficiency
MedGen UID:
333882
Concept ID:
C1841651
Disease or Syndrome
Glomerulonephritis with sparse hair and telangiectases
MedGen UID:
374835
Concept ID:
C1841989
Disease or Syndrome
Focal segmental glomerulosclerosis 3, susceptibility to
MedGen UID:
335850
Concept ID:
C1842982
Finding
Focal segmental glomerulosclerosis (FSGS) is a pathologic entity associated clinically with proteinuria, the nephrotic syndrome (NPHS), and progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD) (Meyrier, 2005). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278).
Martin-Probst deafness-mental retardation syndrome
MedGen UID:
375620
Concept ID:
C1845285
Disease or Syndrome
Amme complex
MedGen UID:
337424
Concept ID:
C1846242
Disease or Syndrome
Methylmalonic acidemia with homocystinuria
MedGen UID:
341256
Concept ID:
C1848561
Disease or Syndrome
The clinical manifestations of disorders of intracellular cobalamin metabolism can be highly variable even within a single complementation group. The prototype and best understood is cblC; it is also the most common of these disorders. The age of initial presentation of cblC spans a wide range, including: Newborns, who can have intrauterine growth retardation (IUGR) and microcephaly; Infants, who can have poor feeding, failure to thrive, pallor, and neurologic signs, and occasionally hemolytic uremic syndrome (HUS) and/or seizures including infantile spasms; Toddlers, who can have failure to thrive, poor head growth, cytopenias (including megaloblastic anemia), global developmental delay, encephalopathy, and neurologic signs such as hypotonia and seizures; and Adolescents and adults, who can have neuropsychiatric symptoms, progressive cognitive decline, and/or subacute combined degeneration of the spinal cord.
Vascular hyalinosis
MedGen UID:
376398
Concept ID:
C1848590
Disease or Syndrome
Oculorenocerebellar syndrome
MedGen UID:
340516
Concept ID:
C1850331
Disease or Syndrome
Nephrosis deafness urinary tract digital malformation
MedGen UID:
340568
Concept ID:
C1850552
Disease or Syndrome
Nephropathy deafness hyperparathyroidism
MedGen UID:
340569
Concept ID:
C1850553
Disease or Syndrome
Familial mediterranean fever, autosomal dominant
MedGen UID:
341987
Concept ID:
C1851347
Disease or Syndrome
Dyschondrosteosis nephritis
MedGen UID:
342135
Concept ID:
C1851986
Disease or Syndrome
Cryoglobulinemia, familial mixed
MedGen UID:
343814
Concept ID:
C1852456
Disease or Syndrome
Renal coloboma syndrome
MedGen UID:
339002
Concept ID:
C1852759
Disease or Syndrome
Renal coloboma (papillorenal syndrome) is an autosomal dominant condition characterized by renal hypodysplasia and abnormalities of the optic nerve. Abnormal renal structure or function is noted in 92% of affected individuals; ophthalmologic abnormalities are noted in 77% of affected individuals who have pathogenic variants in PAX2. Renal abnormalities can be clinically silent in rare individuals. In most individuals, clinically significant renal insufficiency/renal failure is reported. End-stage renal disease requiring renal transplant is not uncommon. Ophthalmologic abnormalities are typically described as optic nerve coloboma or dysplasia. Iris colobomas have not been reported in any individual with a PAX2 pathogenic variant. Ophthalmologic abnormalities may significantly impair vision in some individuals, while others have subtle changes only noted after detailed ophthalmologic examination. Additional clinical findings include hearing loss, which is noted in 7% of individuals with identified pathogenic variants in PAX2.
Nephrotic syndrome, type 3
MedGen UID:
377831
Concept ID:
C1853124
Disease or Syndrome
Nephrotic syndrome, a malfunction of the glomerular filter, is characterized clinically by proteinuria, edema, and end-stage renal disease (ESRD). Renal histopathology may show diffuse mesangial sclerosis (DMS) or focal segmental glomerulosclerosis (FSGS) (Hinkes et al., 2006). Most patients with NPHS3 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen (Gbadegesin et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (256300).
Limb deficiencies distal with micrognathia
MedGen UID:
343368
Concept ID:
C1855500
Disease or Syndrome
Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients with SHFM3 have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting (Elliott and Evans, 2006). For additional phenotypic information and a discussion of genetic heterogeneity in this disorder, see SHFM1 (183600).
Donnai Barrow syndrome
MedGen UID:
347406
Concept ID:
C1857277
Disease or Syndrome
Donnai-Barrow syndrome (DBS) is characterized by typical craniofacial features (ocular hypertelorism, enlarged fontanelle), ocular findings (high myopia, retinal detachment, progressive vision loss, and iris coloboma), sensorineural hearing loss, agenesis of the corpus callosum, intellectual disability, and congenital diaphragmatic hernia (CDH) and/or omphalocele. Both inter- and intrafamilial phenotypic variability are observed.
Deafness, cochlear, with myopia and intellectual impairment
MedGen UID:
347430
Concept ID:
C1857342
Disease or Syndrome
Deafness and myopia (DFNMYP) syndrome is characterized by moderate-profound, bilateral, congenital or prelingual deafness (sensorineural hearing loss or auditory neuropathy spectrum disorder) and high myopia (>-6 diopters). In individuals with a molecularly confirmed diagnosis reported to date, hearing loss was progressive and severity ranged from moderate to profound. Vestibular testing was normal. Myopia was diagnosed at infancy or early childhood.
Pyogenic arthritis, pyoderma gangrenosum and acne
MedGen UID:
346801
Concept ID:
C1858361
Disease or Syndrome
Focal segmental glomerulosclerosis 2
MedGen UID:
349053
Concept ID:
C1858915
Disease or Syndrome
Focal segmental glomerulosclerosis (FSGS) is a pathologic entity associated clinically with proteinuria, the nephrotic syndrome (NPHS), and progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD) (review by Meyrier, 2005). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome (NPHS), see FSGS1 (603278).
Chondroitin-6-sulfaturia, defective cellular immunity, nephrotic syndrome
MedGen UID:
349095
Concept ID:
C1859104
Disease or Syndrome
Feigenbaum Bergeron Richardson syndrome
MedGen UID:
349198
Concept ID:
C1859596
Disease or Syndrome
Vasculopathy, retinal, with cerebral leukodystrophy
MedGen UID:
348124
Concept ID:
C1860518
Disease or Syndrome
Retinal vasculopathy with cerebral leukodystrophy is an adult-onset autosomal dominant disorder involving the microvessels of the brain and resulting in central nervous system degeneration with progressive loss of vision, stroke, motor impairment, and cognitive decline. Death occurs in most patients 5 to 10 years after onset. A subset of affected individuals have systemic vascular involvement evidenced by Raynaud's phenomenon, micronodular cirrhosis, and glomerular dysfunction (summary by Richards et al., 2007).
Majeed syndrome
MedGen UID:
351273
Concept ID:
C1864997
Disease or Syndrome
Majeed syndrome is characterized by: Chronic recurrent multifocal osteomyelitis (CRMO) that is of early onset with a lifelong course; and Congenital dyserythropoietic anemia (CDA) that presents as hypochromic, microcytic anemia during the first year of life and ranges from mild to transfusion dependent. Some individuals also develop a transient inflammatory dermatosis, often manifesting as Sweet syndrome (neutrophilic skin infiltration).
Glomerulopathy with fibronectin deposits 2
MedGen UID:
356149
Concept ID:
C1866075
Disease or Syndrome
Glomerulopathy with fibronectin deposits is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life. Pathologic examination shows enlarged glomeruli with mesangial and subendothelial fibrillary deposits that show strong immunoreactivity to fibronectin (Castelletti et al., 2008). For a discussion of genetic heterogeneity of GFND, see 137950.
Spastic paraplegia, sensorineural deafness, mental retardation, and progressive nephropathy
MedGen UID:
355816
Concept ID:
C1866853
Disease or Syndrome
Pheochromocytoma-islet cell tumor syndrome
MedGen UID:
401431
Concept ID:
C1868392
Neoplastic Process
Nephrotic syndrome, idiopathic, steroid-resistant
MedGen UID:
358380
Concept ID:
C1868672
Disease or Syndrome
Steroid-resistant nephrotic syndrome type 2 is an autosomal recessive disorder characterized clinically by childhood onset of proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Kidney biopsies show nonspecific histologic changes such as minimal change, focal segmental glomerulosclerosis (FSGS), and diffuse mesangial proliferation. The disorder is resistant to steroid treatment and progresses to end-stage renal failure in the first or second decades (summary by Fuchshuber et al., 1996). Some patients show later onset of the disorder (Tsukaguchi et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (256300).
Gaucher's disease, type 1
MedGen UID:
409531
Concept ID:
C1961835
Disease or Syndrome
Gaucher disease (GD) encompasses a continuum of clinical findings from a perinatal lethal disorder to an asymptomatic type. The identification of three major clinical types (1, 2, and 3) and two other subtypes (perinatal-lethal and cardiovascular) is useful in determining prognosis and management. GD type 1 is characterized by the presence of clinical or radiographic evidence of bone disease (osteopenia, focal lytic or sclerotic lesions, and osteonecrosis), hepatosplenomegaly, anemia and thrombocytopenia, lung disease, and the absence of primary central nervous system disease. GD types 2 and 3 are characterized by the presence of primary neurologic disease; in the past, they were distinguished by age of onset and rate of disease progression, but these distinctions are not absolute. Disease with onset before age two years, limited psychomotor development, and a rapidly progressive course with death by age two to four years is classified as GD type 2. Individuals with GD type 3 may have onset before age two years, but often have a more slowly progressive course, with survival into the third or fourth decade. The perinatal-lethal form is associated with ichthyosiform or collodion skin abnormalities or with nonimmune hydrops fetalis. The cardiovascular form is characterized by calcification of the aortic and mitral valves, mild splenomegaly, corneal opacities, and supranuclear ophthalmoplegia. Cardiopulmonary complications have been described with all the clinical subtypes, although varying in frequency and severity.
Lipoprotein glomerulopathy
MedGen UID:
382034
Concept ID:
C2673196
Disease or Syndrome
Lipoprotein glomerulopathy is an uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries (Saito et al., 2006). It mainly affects people of Japanese and Chinese origin; in these populations, it is associated with mutations in the gene that encodes apolipoprotein E (APOE; 107741). The disorder had rarely been described in Caucasians.
Multicentric osteolysis nephropathy
MedGen UID:
436237
Concept ID:
C2674705
Disease or Syndrome
Multicentric carpotarsal osteolysis syndrome is a rare skeletal disorder, usually presenting in early childhood with a clinical picture mimicking juvenile rheumatoid arthritis. Progressive destruction of the carpal and tarsal bone usually occurs and other bones may also be involved. Chronic renal failure is a frequent component of the syndrome. Mental retardation and minor facial anomalies have been noted in some patients. Autosomal dominant inheritance has been documented in many families (Pai and Macpherson, 1988). See also Torg-Winchester syndrome (259600), an autosomal recessive multicentric osteolysis syndrome.
Atypical hemolytic-uremic syndrome 6
MedGen UID:
414541
Concept ID:
C2752036
Finding
Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. Typical (acquired) HUS is triggered by infectious agents such as strains of E. coli (Stx-E. coli) that produce powerful Shiga-like exotoxins, whereas atypical HUS (aHUS) can be genetic, acquired, or idiopathic (of unknown cause). Onset of atypical HUS ranges from prenatal to adulthood. Individuals with genetic atypical HUS frequently experience relapse even after complete recovery following the presenting episode. Sixty percent of genetic aHUS progresses to end-stage renal disease (ESRD).
Atypical hemolytic-uremic syndrome 5
MedGen UID:
442875
Concept ID:
C2752037
Finding
Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. Typical (acquired) HUS is triggered by infectious agents such as strains of E. coli (Stx-E. coli) that produce powerful Shiga-like exotoxins, whereas atypical HUS (aHUS) can be genetic, acquired, or idiopathic (of unknown cause). Onset of atypical HUS ranges from prenatal to adulthood. Individuals with genetic atypical HUS frequently experience relapse even after complete recovery following the presenting episode. Sixty percent of genetic aHUS progresses to end-stage renal disease (ESRD).
Atypical hemolytic-uremic syndrome 4
MedGen UID:
416691
Concept ID:
C2752038
Finding
Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. Typical (acquired) HUS is triggered by infectious agents such as strains of E. coli (Stx-E. coli) that produce powerful Shiga-like exotoxins, whereas atypical HUS (aHUS) can be genetic, acquired, or idiopathic (of unknown cause). Onset of atypical HUS ranges from prenatal to adulthood. Individuals with genetic atypical HUS frequently experience relapse even after complete recovery following the presenting episode. Sixty percent of genetic aHUS progresses to end-stage renal disease (ESRD).
Atypical hemolytic-uremic syndrome 3
MedGen UID:
414542
Concept ID:
C2752039
Finding
Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. Typical (acquired) HUS is triggered by infectious agents such as strains of E. coli (Stx-E. coli) that produce powerful Shiga-like exotoxins, whereas atypical HUS (aHUS) can be genetic, acquired, or idiopathic (of unknown cause). Onset of atypical HUS ranges from prenatal to adulthood. Individuals with genetic atypical HUS frequently experience relapse even after complete recovery following the presenting episode. Sixty percent of genetic aHUS progresses to end-stage renal disease (ESRD).
Atypical hemolytic-uremic syndrome 2
MedGen UID:
414167
Concept ID:
C2752040
Finding
Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. Typical (acquired) HUS is triggered by infectious agents such as strains of E. coli (Stx-E. coli) that produce powerful Shiga-like exotoxins, whereas atypical HUS (aHUS) can be genetic, acquired, or idiopathic (of unknown cause). Onset of atypical HUS ranges from prenatal to adulthood. Individuals with genetic atypical HUS frequently experience relapse even after complete recovery following the presenting episode. Sixty percent of genetic aHUS progresses to end-stage renal disease (ESRD).
Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis
MedGen UID:
462559
Concept ID:
C3151209
Disease or Syndrome
HUPRA syndrome is a severe autosomal recessive multisystem disorder characterized by onset in infancy of progressive renal failure leading to electrolyte imbalances, metabolic alkalosis, pulmonary hypertension, hypotonia, and delayed development. Affected individuals are born prematurely (summary by Belostotsky et al., 2011).
Lipodystrophy, partial, acquired, with low complement component c3, with or without glomerulonephritis
MedGen UID:
462697
Concept ID:
C3151347
Disease or Syndrome
Acquired partial lipodystrophy (APLD) is characterized clinically by the gradual onset of bilaterally symmetrical loss of subcutaneous fat from the face, neck, upper extremities, thorax, and abdomen, in the 'cephalocaudal' sequence, sparing the lower extremities. A large group of patients (83%) with acquired partial lipodystrophy have low serum levels of complement component C3 due to the presence of C3 nephritic factor, an IgG antibody that causes continuous activation of the alternative complement pathway and consumption of serum C3. About 22% of patients with this acquired complement defect develop membranoproliferative glomerulonephritis. Some individuals may also show an increased risk of infection (Misra et al., 2004). Acquired partial lipodystrophy is not inherited in a classic mendelian pattern; it rather represents a phenotype with a complex etiology. Affected individuals may have genetic susceptibility factors that require the additional presence of environmental factors or acquired disorders to be expressed (summary by Hegele et al., 2006). Most cases are sporadic, family history is negative, and females are more often affected than males (ratio, 4:1) (summary by Misra et al., 2004). See 608709 for a subtype of APLD not associated with low complement C3 or renal disease.
Iga nephropathy 2
MedGen UID:
462728
Concept ID:
C3151378
Finding
Focal segmental glomerulosclerosis 6
MedGen UID:
481535
Concept ID:
C3279905
Disease or Syndrome
Focal segmental glomerulosclerosis-6 is an autosomal recessive childhood-onset kidney disorder manifest clinically by the nephrotic syndrome, which is characterized by proteinuria, hematuria, hypoalbuminemia, and progressive renal failure. It is a disease of the glomerular podocyte (summary by Mele et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278).
Nephrotic syndrome, type 6
MedGen UID:
481730
Concept ID:
C3280100
Disease or Syndrome
The nephrotic syndrome refers to a genetically heterogeneous group of disorders characterized by proteinuria, hypoalbuminemia, and edema, resulting in end-stage kidney disease if untreated. Inherited defects in podocyte structure and function have been observed in some children with the steroid-resistant subtype of nephrotic syndrome (summary by Ozaltin et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Nephrotic syndrome, type 5, with or without ocular abnormalities
MedGen UID:
481743
Concept ID:
C3280113
Disease or Syndrome
Nephrotic syndrome type 5 is an autosomal recessive disorder characterized by very early onset of progressive renal failure manifest as proteinuria with consecutive edema starting in utero or within the first 3 months of life. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus (summary by Hasselbacher et al., 2006). Mutation in the LAMB2 gene can also caused Pierson syndrome (609049), which is characterized by nephrotic syndrome, distinct ocular anomalies, namely microcoria, and neurodevelopmental delay. For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Asphyxiating thoracic dystrophy 5
MedGen UID:
482228
Concept ID:
C3280598
Disease or Syndrome
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500).
Charcot-Marie-Tooth disease, dominant intermediate E
MedGen UID:
482475
Concept ID:
C3280845
Disease or Syndrome
Autosomal dominant intermediate Charcot-Marie-Tooth disease E with focal segmental glomerulonephritis is characterized by the neurologic features of CMT, including distal muscle weakness and atrophy and distal sensory loss, and the features of FSGS, including proteinuria, progression to end-stage renal disease, and a characteristic histologic pattern on renal biopsy (summary by Boyer et al., 2011). Isolated focal segmental glomerulosclerosis-5 (FSGS5; 613237) is also caused by heterozygous mutation in the INF2 gene. For a discussion of genetic heterogeneity of CMTDI, see 606482.
Familial steroid-resistant nephrotic syndrome with sensorineural deafness
MedGen UID:
766263
Concept ID:
C3553349
Disease or Syndrome
COENZYME Q10 DEFICIENCY, PRIMARY, 3
MedGen UID:
766272
Concept ID:
C3553358
Disease or Syndrome
INTERSTITIAL NEPHRITIS, KARYOMEGALIC
MedGen UID:
766688
Concept ID:
C3553774
Disease or Syndrome
NEPHROTIC SYNDROME, TYPE 7
MedGen UID:
767244
Concept ID:
C3554330
Disease or Syndrome
HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 7
MedGen UID:
814949
Concept ID:
C3808619
Finding
AHUS, SUSCEPTIBILITY TO, 7
MedGen UID:
814950
Concept ID:
C3808620
Finding
NEPHROTIC SYNDROME, TYPE 8
MedGen UID:
815283
Concept ID:
C3808953
Disease or Syndrome
NEPHROTIC SYNDROME, TYPE 9
MedGen UID:
816295
Concept ID:
C3809965
Disease or Syndrome
FANCONI RENOTUBULAR SYNDROME 3
MedGen UID:
816430
Concept ID:
C3810100
Disease or Syndrome
Adolescent nephronophthisis
MedGen UID:
346809
Concept ID:
C1858392
Disease or Syndrome
Nephronophthisis is a disorder that affects the kidneys. It is characterized by inflammation and scarring (fibrosis) that impairs kidney function. These abnormalities lead to increased urine production (polyuria), excessive thirst (polydipsia), general weakness, and extreme tiredness (fatigue). In addition, affected individuals develop fluid-filled cysts in the kidneys, usually in an area known as the corticomedullary region. Another feature of nephronophthisis is a shortage of red blood cells, a condition known as anemia. Nephronophthisis eventually leads to end-stage renal disease (ESRD), a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively. Nephronophthisis can be classified by the approximate age at which ESRD begins: around age 1 (infantile), around age 13 (juvenile), and around age 19 (adolescent). About 85 percent of all cases of nephronophthisis are isolated, which means they occur without other signs and symptoms. Some people with nephronophthisis have additional features, which can include liver fibrosis, heart abnormalities, or mirror image reversal of the position of one or more organs inside the body (situs inversus). Nephronophthisis can occur as part of separate syndromes that affect other areas of the body; these are often referred to as nephronophthisis-associated ciliopathies. For example, Senior-Løken syndrome is characterized by the combination of nephronophthisis and a breakdown of the light-sensitive tissue at the back of the eye (retinal degeneration); Joubert syndrome affects many parts of the body, causing neurological problems and other features, which can include nephronophthisis.

Recent clinical studies

Etiology

Khedr E, El Sharkawy M, El Shahawy Y, Sany D, Sayed H
Saudi J Kidney Dis Transpl 2015 Jan;26(1):161-7. PMID: 25579742
Hsu YC, Lei CC, Shih YH, Ho C, Lin CL
Am J Med Sci 2015 Feb;349(2):162-8. doi: 10.1097/MAJ.0000000000000352. PMID: 25474224
Zhang C, Zhang W, Chen HM, Liu C, Wu J, Shi S, Liu ZH
Am J Kidney Dis 2015 Feb;65(2):223-32. Epub 2014 Sep 11 doi: 10.1053/j.ajkd.2014.07.013. [Epub ahead of print] PMID: 25218681
Talreja H, Akbari A, White CA, Ramsay TO, Hiremath S, Knoll G
Am J Kidney Dis 2014 Dec;64(6):962-8. Epub 2014 Oct 8 doi: 10.1053/j.ajkd.2014.07.027. [Epub ahead of print] PMID: 25304983
Nagai K, Yamagata K, Ohkubo R, Saito C, Asahi K, Iseki K, Kimura K, Moriyama T, Narita I, Fujimoto S, Tsuruya K, Konta T, Kondo M, Watanabe T
Nephrology (Carlton) 2014 Sep;19(9):574-80. doi: 10.1111/nep.12286. PMID: 24899111

Diagnosis

Shiraishi N, Kitamura K, Hayata M, Ogata T, Tajiri-Okamura K, Nakayama Y, Kohda Y, Tomita K, Mukoyama M
Am J Kidney Dis 2015 Mar;65(3):490-3. Epub 2014 Dec 24 doi: 10.1053/j.ajkd.2014.09.028. [Epub ahead of print] PMID: 25542412
Zhang C, Zhang W, Chen HM, Liu C, Wu J, Shi S, Liu ZH
Am J Kidney Dis 2015 Feb;65(2):223-32. Epub 2014 Sep 11 doi: 10.1053/j.ajkd.2014.07.013. [Epub ahead of print] PMID: 25218681
Talreja H, Akbari A, White CA, Ramsay TO, Hiremath S, Knoll G
Am J Kidney Dis 2014 Dec;64(6):962-8. Epub 2014 Oct 8 doi: 10.1053/j.ajkd.2014.07.027. [Epub ahead of print] PMID: 25304983
Nagai K, Yamagata K, Ohkubo R, Saito C, Asahi K, Iseki K, Kimura K, Moriyama T, Narita I, Fujimoto S, Tsuruya K, Konta T, Kondo M, Watanabe T
Nephrology (Carlton) 2014 Sep;19(9):574-80. doi: 10.1111/nep.12286. PMID: 24899111
Zhai Y, Xu H, Shen Q, Cao Q, Zhu G, Wei M, Sun L, Liu H, Rao J, Fang X, Chen J, Guo W
Nephrology (Carlton) 2014 Jul;19(7):426-31. doi: 10.1111/nep.12260. PMID: 24720478

Therapy

Khedr E, El Sharkawy M, El Shahawy Y, Sany D, Sayed H
Saudi J Kidney Dis Transpl 2015 Jan;26(1):161-7. PMID: 25579742
Hsu YC, Lei CC, Shih YH, Ho C, Lin CL
Am J Med Sci 2015 Feb;349(2):162-8. doi: 10.1097/MAJ.0000000000000352. PMID: 25474224
Talreja H, Akbari A, White CA, Ramsay TO, Hiremath S, Knoll G
Am J Kidney Dis 2014 Dec;64(6):962-8. Epub 2014 Oct 8 doi: 10.1053/j.ajkd.2014.07.027. [Epub ahead of print] PMID: 25304983
Huang L, You YS, Wu W
Ren Fail 2014 Sep;36(8):1328-32. Epub 2014 Jul 2 doi: 10.3109/0886022X.2014.934177. [Epub ahead of print] PMID: 24986244
Wu MT, Tung SC, Hsu KT, Lee CT
J Renin Angiotensin Aldosterone Syst 2014 Sep;15(3):271-7. Epub 2012 Dec 7 doi: 10.1177/1470320312467560. [Epub ahead of print] PMID: 23223162

Prognosis

Khedr E, El Sharkawy M, El Shahawy Y, Sany D, Sayed H
Saudi J Kidney Dis Transpl 2015 Jan;26(1):161-7. PMID: 25579742
Zhang C, Zhang W, Chen HM, Liu C, Wu J, Shi S, Liu ZH
Am J Kidney Dis 2015 Feb;65(2):223-32. Epub 2014 Sep 11 doi: 10.1053/j.ajkd.2014.07.013. [Epub ahead of print] PMID: 25218681
Talreja H, Akbari A, White CA, Ramsay TO, Hiremath S, Knoll G
Am J Kidney Dis 2014 Dec;64(6):962-8. Epub 2014 Oct 8 doi: 10.1053/j.ajkd.2014.07.027. [Epub ahead of print] PMID: 25304983
Nagai K, Yamagata K, Ohkubo R, Saito C, Asahi K, Iseki K, Kimura K, Moriyama T, Narita I, Fujimoto S, Tsuruya K, Konta T, Kondo M, Watanabe T
Nephrology (Carlton) 2014 Sep;19(9):574-80. doi: 10.1111/nep.12286. PMID: 24899111
Inker LA, Levey AS, Pandya K, Stoycheff N, Okparavero A, Greene T; Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
Am J Kidney Dis 2014 Jul;64(1):74-85. Epub 2014 Apr 29 doi: 10.1053/j.ajkd.2014.02.020. [Epub ahead of print] PMID: 24787763Free PMC Article

Clinical prediction guides

Zhang C, Zhang W, Chen HM, Liu C, Wu J, Shi S, Liu ZH
Am J Kidney Dis 2015 Feb;65(2):223-32. Epub 2014 Sep 11 doi: 10.1053/j.ajkd.2014.07.013. [Epub ahead of print] PMID: 25218681
Talreja H, Akbari A, White CA, Ramsay TO, Hiremath S, Knoll G
Am J Kidney Dis 2014 Dec;64(6):962-8. Epub 2014 Oct 8 doi: 10.1053/j.ajkd.2014.07.027. [Epub ahead of print] PMID: 25304983
Masimango MI, Sumaili EK, Jadoul M, Wallemacq P, Mubagwa DK, Makulo RJ, Lepira FB, Nseka NM
BMC Nephrol 2014 Sep 5;15:146. doi: 10.1186/1471-2369-15-146. [Epub ahead of print] PMID: 25189092Free PMC Article
Nagai K, Yamagata K, Ohkubo R, Saito C, Asahi K, Iseki K, Kimura K, Moriyama T, Narita I, Fujimoto S, Tsuruya K, Konta T, Kondo M, Watanabe T
Nephrology (Carlton) 2014 Sep;19(9):574-80. doi: 10.1111/nep.12286. PMID: 24899111
Inker LA, Levey AS, Pandya K, Stoycheff N, Okparavero A, Greene T; Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
Am J Kidney Dis 2014 Jul;64(1):74-85. Epub 2014 Apr 29 doi: 10.1053/j.ajkd.2014.02.020. [Epub ahead of print] PMID: 24787763Free PMC Article

Recent systematic reviews

Inker LA, Levey AS, Pandya K, Stoycheff N, Okparavero A, Greene T; Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
Am J Kidney Dis 2014 Jul;64(1):74-85. Epub 2014 Apr 29 doi: 10.1053/j.ajkd.2014.02.020. [Epub ahead of print] PMID: 24787763Free PMC Article
Geng DF, Sun WF, Yang L, En G, Wang JF
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