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Hepatic failure

MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
Synonyms: Liver failure
SNOMED CT: Liver failure (59927004); Hepatic failure (59927004); Liver function failure (59927004); Liver decompensation (59927004)
 
HPO: HP:0001399

Definition

A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase. [from NCI]

Conditions with this feature

Glycogen storage disease, type IV
MedGen UID:
6642
Concept ID:
C0017923
Disease or Syndrome
The clinical manifestations of glycogen storage disease type IV (GSD IV) discussed in this entry span a continuum of different subtypes with variable ages of onset, severity, and clinical features. Clinical findings vary extensively both within and between families. The fatal perinatal neuromuscular subtype presents in utero with fetal akinesia deformation sequence (FADS) with decreased fetal movements, polyhydramnios, and fetal hydrops. Death usually occurs in the neonatal period. The congenital neuromuscular subtype presents in the newborn period with profound hypotonia, respiratory distress, and dilated cardiomyopathy. Death usually occurs in early infancy. Infants with the classic (progressive) hepatic subtype may appear normal at birth, but rapidly develop failure to thrive; hepatomegaly, liver dysfunction, and progressive liver cirrhosis; hypotonia; and cardiomyopathy. Without liver transplantation, death from liver failure usually occurs by age five years. Children with the non-progressive hepatic subtype tend to present with hepatomegaly, liver dysfunction, myopathy, and hypotonia; however, they are likely to survive without progression of the liver disease and may not show cardiac, skeletal muscle, or neurologic involvement. The childhood neuromuscular subtype is rare and the course is variable, ranging from onset in the second decade with a mild disease course to a more severe, progressive course resulting in death in the third decade.
Wilson 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 older than 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.
Neuronal ceroid lipofuscinosis
MedGen UID:
10326
Concept ID:
C0027877
Disease or Syndrome
The neuronal ceroid-lipofuscinoses (NCLs) are a group of inherited, neurodegenerative, lysosomal storage disorders characterized by progressive intellectual and motor deterioration, seizures, and early death. Visual loss is a feature of most forms. Clinical phenotypes have been characterized traditionally according to the age of onset and order of appearance of clinical features into infantile, late-infantile, juvenile, adult, and Northern epilepsy (also known as progressive epilepsy with mental retardation [EPMR]). There is however genetic and allelic heterogeneity; a proposed new nomenclature and classification system has been developed to take into account both the responsible gene and the age at disease onset; for example, CLN1 disease, infantile onset and CLN1 disease, juvenile onset are both caused by pathogenic variants in PPT1 but with differing age of onset. The most prevalent NCLs are CLN3 disease, classic juvenile and CLN2 disease, classic late infantile (although prevalence varies by ethnicity and country of family origin): CLN2 disease, classic late infantile. The first symptoms typically appear between age two and four years, usually starting with epilepsy, followed by regression of developmental milestones, myoclonic ataxia, and pyramidal signs. Visual impairment typically appears at age four to six years and rapidly progresses to light /dark awareness only. Life expectancy ranges from age six years to early teenage. CLN3 disease, classic juvenile. Onset is usually between ages four and ten years. Rapidly progressing visual loss resulting in severe visual impairment within one to two years is often the first clinical sign. Epilepsy with generalized tonic-clonic seizures and/or complex-partial seizures typically appears around age ten years. Life expectancy ranges from the late teens to the 30s. Other forms of NCL may present with behavior changes, epilepsy, visual impairment, or slowing of developmental progress and then loss of skills. The course may be extremely variable. Some genotype-phenotype information is available.
Erythropoietic protoporphyria
MedGen UID:
56455
Concept ID:
C0162568
Disease or Syndrome
Erythropoietic protoporphyria (EPP) is characterized by cutaneous photosensitivity (usually beginning in infancy or childhood) that results in tingling, burning, pain, and itching within 30 minutes after exposure to sun or ultraviolet light and may be accompanied by swelling and redness. Symptoms (which may seem out of proportion to the visible skin lesions) may persist for hours or days after the initial phototoxic reaction. Photosensitivity remains for life. Multiple episodes of acute photosensitivity may lead to chronic changes of sun-exposed skin (lichenification, leathery pseudovesicles, grooving around the lips) and loss of lunulae of the nails. Approximately 20%-30% of individuals with EPP have some degree of liver dysfunction, which is typically mild with slight elevations of the liver enzymes. Up to 5% may develop more advanced liver disease which may be accompanied by motor neuropathy similar to that seen in the acute porphyrias.
Progressive sclerosing poliodystrophy
MedGen UID:
60012
Concept ID:
C0205710
Disease or Syndrome
POLG-related disorders comprise a continuum of overlapping phenotypes that were clinically defined long before their molecular basis was known. Most affected individuals have some, but not all, of the features of a given phenotype; nonetheless, the following nomenclature can assist the clinician in diagnosis and management. Onset of the POLG-related disorders ranges from infancy to late adulthood. Alpers-Huttenlocher syndrome (AHS), one of the most severe phenotypes, is characterized by childhood-onset progressive and ultimately severe encephalopathy with intractable epilepsy and hepatic failure. Childhood myocerebrohepatopathy spectrum (MCHS) presents between the first few months of life and about age three years with developmental delay or dementia, lactic acidosis, and a myopathy with failure to thrive. Other findings can include liver failure, renal tubular acidosis, pancreatitis, cyclic vomiting, and hearing loss. Myoclonic epilepsy myopathy sensory ataxia (MEMSA) now describes the spectrum of disorders with epilepsy, myopathy, and ataxia without ophthalmoplegia. MEMSA now includes the disorders previously described as spinocerebellar ataxia with epilepsy (SCAE). The ataxia neuropathy spectrum (ANS) includes the phenotypes previously referred to as mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). About 90% of persons in the ANS have ataxia and neuropathy as core features. Approximately two thirds develop seizures and almost one half develop ophthalmoplegia; clinical myopathy is rare. Autosomal recessive progressive external ophthalmoplegia (arPEO) is characterized by progressive weakness of the extraocular eye muscles resulting in ptosis and ophthalmoparesis (or paresis of the extraocular muscles) without associated systemic involvement; however, caution is advised because many individuals with apparently isolated arPEO at the onset develop other manifestations of POLG-related disorders over years or decades. Of note, in the ANS spectrum the neuropathy commonly precedes the onset of PEO by years to decades. Autosomal dominant progressive external ophthalmoplegia (adPEO) typically includes a generalized myopathy and often variable degrees of sensorineural hearing loss, axonal neuropathy, ataxia, depression, parkinsonism, hypogonadism, and cataracts (in what has been called "chronic progressive external ophthalmoplegia plus," or "CPEO+").
Neonatal hemochromatosis
MedGen UID:
82768
Concept ID:
C0268059
Disease or Syndrome
Neonatal hemochromatosis (NH) is characterized by hepatic failure in the newborn period and heavy iron staining in the liver. In addition, there is marked siderosis of extrahepatic tissues, including the heart and pancreas (Driscoll et al., 1988). Whitington (2007) postulated that some cases of neonatal hemochromatosis result from maternal alloimmunity directed at the fetal liver, and therefore do not represent an inherited mendelian disorder. Other causes may result from metabolic disease or perinatal infection. In particular, he commented that the disorder is not related to the family of inherited liver diseases that fall under the classification of hereditary hemochromatosis (see, e.g., 235200). Whitington (2007) proposed the term 'congenital alloimmune hepatitis.' In the past, the disorder has loosely been labeled 'neonatal hepatitis' and 'giant cell hepatitis,' which are pathologic findings in the liver representing a common response to a variety of insults, including cholestatic disorders and infection, among others (Fawaz et al., 1975; Knisely et al., 1987; Kelly et al., 2001).
Fumarase deficiency
MedGen UID:
87458
Concept ID:
C0342770
Disease or Syndrome
Fumarate hydratase deficiency results in severe neonatal and early infantile encephalopathy that is characterized by poor feeding, failure to thrive, hypotonia, lethargy, and seizures. Dysmorphic facial features include frontal bossing, depressed nasal bridge, and widely spaced eyes. Many affected individuals are microcephalic. A spectrum of brain abnormalities are seen on magnetic resonance imaging, including cerebral atrophy, enlarged ventricles and generous extra-axial cerebral spinal fluid (CSF) spaces, delayed myelination for age, thinning of the corpus callosum, and an abnormally small brain stem. Brain malformations including bilateral polymicrogyria and absence of the corpus callosum can also be observed. Development is severely affected: most affected individuals are non-verbal and non-ambulatory, and many die during early childhood. Less severely affected individuals with moderate cognitive impairment and long-term survival have been reported.
Cranioectodermal dysplasia 1
MedGen UID:
96586
Concept ID:
C0432235
Disease or Syndrome
Cranioectodermal dysplasia (CED), a ciliopathy also known as Sensenbrenner syndrome, is a multisystem disorder with skeletal involvement (narrow thorax, shortened proximal limbs, and brachydactyly), ectodermal features (widely-spaced hypoplastic teeth, hypodontia, sparse hair, skin laxity, abnormal nails), joint laxity, growth retardation, and characteristic facial features (frontal bossing, low-set simple ears, high forehead, telecanthus/epicanthus, full cheeks, everted lower lip). Most affected children develop nephronophthisis that often leads to end-stage renal disease (ESRD) in infancy or childhood, a major cause of morbidity and mortality. Hepatic fibrosis and retinal dystrophy, other manifestations of ciliopathies, are also observed. Dolichocephaly, often secondary to sagittal craniosynostosis, is a primary manifestation that distinguishes CED from most other ciliopathies. Brain malformations and developmental delay may also occur.
Lafora disease
MedGen UID:
155631
Concept ID:
C0751783
Disease or Syndrome
Lafora disease (LD) is characterized by fragmentary, symmetric, or generalized myoclonus and/or generalized tonic-clonic seizures, visual hallucinations (occipital seizures), and progressive neurologic degeneration including cognitive and/or behavioral deterioration, dysarthria, and ataxia beginning in previously healthy adolescents between ages 12 and 17 years. The frequency and intractability of seizures increase over time. Status epilepticus is common. Emotional disturbance and confusion are common at or soon after onset of seizures and are followed by dementia. Dysarthria and ataxia appear early, spasticity late. Most affected individuals die within ten years of onset, usually from status epilepticus or from complications related to nervous system degeneration.
Mitochondrial complex I deficiency
MedGen UID:
374101
Concept ID:
C1838979
Disease or Syndrome
Isolated complex I deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders (McFarland et al., 2004; Kirby et al., 2004). It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome (256000), Leber hereditary optic neuropathy (535000), and some forms of Parkinson disease (see 556500) (Loeffen et al., 2000; Pitkanen et al., 1996; Robinson, 1998). Genetic Heterogeneity of Complex I Deficiency Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype-phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible (summary by Haack et al., 2012). However, the majority of cases are caused by mutations in nuclear-encoded genes (Loeffen et al., 2000; Triepels et al., 2001). Complex I deficiency with autosomal recessive inheritance results from mutation in nuclear-encoded subunit genes, including NDUFV1 (161015), NDUFV2 (600532), NDUFS1 (157655), NDUFS2 (602985), NDUFS3 (603846), NDUFS4 (602694), NDUFS6 (603848), NDUFS7 (601825), NDUFS8 (602141), NDUFA2 (602137), NDUFA11 (612638), NDUFAF3 (612911), NDUFA10 (603835), NDUFB3 (603839), NDUFB9 (601445), and the complex I assembly genes NDUFAF2 (609653), NDUFAF4 (611776), NDUFAF5 (612360), NUBPL (613621), NDUFAF1 (606934), TMEM126B (615533), TIMMDC1 (615534), and NDUFA13 (609435). The disorder can also be caused by mutation in other nuclear-encoded genes, including FOXRED1 (613622), ACAD9 (611103; see 611126), and MTFMT (611766; see 256000). X-linked inheritance is observed with mutations in the NDUFA1 (300078) and NDUFB11 (300403) genes. Complex I deficiency with mitochondrial inheritance has been associated with mutation in 6 mitochondrial-encoded components of complex I: MTND1 (516000), MTND2 (516001), MTND3 (516002), MTND4 (516003), MTND5 (516005), MTND6 (516006). Most of these patients have a phenotype of Leber hereditary optic neuropathy (LHON; 535000) or Leigh syndrome (256000). Features of complex I deficiency may also be caused by mutation in other mitochondrial genes, including MTTS2 (590085).
Gaucher disease, perinatal lethal
MedGen UID:
374996
Concept ID:
C1842704
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.
Bile acid synthesis defect, congenital, 1
MedGen UID:
335883
Concept ID:
C1843116
Disease or Syndrome
Congenital defects of bile acid synthesis are autosomal recessive disorders characterized by neonatal onset of progressive liver disease with cholestatic jaundice and malabsorption of lipids and lipid-soluble vitamins from the gastrointestinal tract resulting from a primary failure to synthesize bile acids. Affected infants show failure to thrive and secondary coagulopathy. In most forms of the disorder, there is a favorable response to oral bile acid therapy (summary by Cheng et al., 2003). Genetic Heterogeneity of Congenital Defects in Bile Acid Synthesis There are several disorders that result from defects in bile acid synthesis. See CBAS2 (235555), caused by mutation in the delta(4)-3-oxosteroid 5-beta-reductase gene (AKR1D1; 604741) on chromosome 7q33; CBAS3 (613812), caused by mutation in the 7-alpha hydroxylase gene (CYP7B1; 603711) on chromosome 8q12; CBAS4 (214950), caused by mutation in the AMACR gene (604489) on chromosome 5p13; CBAS5 (616278), caused by mutation in the ABCD3 gene (170995) on chromosome 1p21; and CBAS6 (617308), caused by mutation in the ACOX2 gene (601641) on chromosome 3p14. See also progressive familial intrahepatic cholestasis (PFIC1; 211600), which has a similar phenotype.
Coenzyme Q10 deficiency, primary 1
MedGen UID:
334528
Concept ID:
C1843920
Disease or Syndrome
Primary coenzyme Q10 (CoQ10) deficiency is usually associated with multisystem involvement, including neurologic manifestations such as fatal neonatal encephalopathy with hypotonia; a late-onset slowly progressive multiple-system atrophy-like phenotype (neurodegeneration with autonomic failure and various combinations of parkinsonism and cerebellar ataxia, and pyramidal dysfunction); and dystonia, spasticity, seizures, and intellectual disability. Steroid-resistant nephrotic syndrome (SRNS), the hallmark renal manifestation, is often the initial manifestation either as isolated renal involvement that progresses to end-stage renal disease (ESRD), or associated with encephalopathy (seizures, stroke-like episodes, severe neurologic impairment) resulting in early death. Hypertrophic cardiomyopathy (HCM), retinopathy or optic atrophy, and sensorineural hearing loss can also be seen.
Phosphoenolpyruvate carboxykinase deficiency, mitochondrial
MedGen UID:
376665
Concept ID:
C1849821
Disease or Syndrome
Bile acid synthesis defect, congenital, 2
MedGen UID:
383840
Concept ID:
C1856127
Disease or Syndrome
Congenital bile acid synthesis defect type 2 is a disorder characterized by cholestasis, a condition that impairs the production and release of a digestive fluid called bile from liver cells. Bile is used during digestion to absorb fats and fat-soluble vitamins, such as vitamins A, D, E, and K. People with congenital bile acid synthesis defect type 2 cannot produce (synthesize) bile acids, which are a component of bile that stimulate bile flow and help it absorb fats and fat-soluble vitamins. As a result, an abnormal form of bile is produced.The signs and symptoms of congenital bile acid synthesis defect type 2 often develop in infancy. Affected infants usually have a failure to gain weight and grow at the expected rate (failure to thrive) and yellowing of the skin and eyes (jaundice) due to impaired bile flow and a buildup of partially formed bile. Excess fat in the feces (steatorrhea) is another feature of congenital bile acid synthesis defect type 2. As the condition progresses, affected individuals can develop liver abnormalities including inflammation or chronic liver disease (cirrhosis). Some individuals with congenital bile acid synthesis defect type 2 cannot absorb certain fat-soluble vitamins, which can result in softening and weakening of the bones (rickets) or problems with blood clotting that lead to prolonged bleeding.If left untreated, congenital bile acid synthesis defect type 2 typically leads to cirrhosis and death in childhood.
Urioste Martinez-Frias syndrome
MedGen UID:
343489
Concept ID:
C1856159
Disease or Syndrome
Trichohepatoenteric syndrome
MedGen UID:
347405
Concept ID:
C1857276
Disease or Syndrome
Although the spectrum of phenotypic expression in trichohepatoenteric syndrome (THES) is broad, the characteristic features include intrauterine growth retardation, woolly hair, facial dysmorphism, intractable diarrhea in infancy requiring total parenteral nutrition, and immunodepression. Hepatic involvement contributes to the poor prognosis of affected patients (summary by Fabre et al., 2007). Genetic Heterogeneity of Trichohepatoenteric Syndrome Trichohepatoenteric syndrome-2 (THES2; 614602) is caused by mutation in the SKIV2L gene (600478) on chromosome 6p21.
Bile acid synthesis defect, congenital, 4
MedGen UID:
388039
Concept ID:
C1858328
Disease or Syndrome
Berry aneurysm, cirrhosis, pulmonary emphysema, and cerebral calcification
MedGen UID:
347170
Concept ID:
C1859519
Disease or Syndrome
Congenital disorder of glycosylation type 1B
MedGen UID:
400692
Concept ID:
C1865145
Disease or Syndrome
Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. Type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein. These disorders can be identified by a characteristic abnormal isoelectric focusing profile of plasma transferrin (Leroy, 2006). For a discussion of the classification of CDGs, see CDG1A (212065). CDG Ib is clinically distinct from most other CDGs by the lack of significant central nervous system involvement. The predominant symptoms are chronic diarrhea with failure to thrive and protein-losing enteropathy with coagulopathy. Some patients develop hepatic fibrosis. CDG Ib is also different from other CDGs in that it can be treated effectively with oral mannose supplementation, but can be fatal if untreated (Marquardt and Denecke, 2003). Thus, CDG Ib should be considered in the differential diagnosis of patients with unexplained hypoglycemia, chronic diarrhea, liver disease, or coagulopathy in order to allow early diagnosis and effective therapy (Vuillaumier-Barrot et al., 2002) Freeze and Aebi (1999) reviewed CDG Ib and CDG Ic (603147). Marques-da-Silva et al. (2017) systematically reviewed the literature concerning liver involvement in CDG.
Acyl-CoA dehydrogenase family, member 9, deficiency of
MedGen UID:
370195
Concept ID:
C1970173
Disease or Syndrome
ACAD9 deficiency is an autosomal recessive multisystem disorder characterized by infantile onset of acute metabolic acidosis, hypertrophic cardiomyopathy, and muscle weakness associated with a deficiency of mitochondrial complex I activity in muscle, liver, and fibroblasts (summary by Haack et al., 2010). For a general description and a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010.
Progressive familial intrahepatic cholestasis 4
MedGen UID:
418976
Concept ID:
C2931067
Disease or Syndrome
Bile acid synthesis defect, congenital, 3
MedGen UID:
462497
Concept ID:
C3151147
Disease or Syndrome
Mitochondrial DNA-depletion syndrome 3, hepatocerebral
MedGen UID:
462863
Concept ID:
C3151513
Disease or Syndrome
The two forms of deoxyguanosine kinase (DGUOK) deficiency are a neonatal multisystem disorder and an isolated hepatic disorder that presents later in infancy or childhood. The majority of affected individuals have the multisystem illness with hepatic disease (jaundice, cholestasis, hepatomegaly, and elevated transaminases) and neurologic manifestations (hypotonia, nystagmus, and psychomotor retardation) evident within weeks of birth. Those with isolated liver disease may also have renal involvement and some later develop mild hypotonia. Progressive hepatic disease is the most common cause of death in both forms.
Peroxisome biogenesis disorder 12A
MedGen UID:
766916
Concept ID:
C3554002
Disease or Syndrome
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 14 (CG14, equivalent to CGJ) have mutations in the PEX19 gene. For information on the history of PBD complementation groups, see 214100.
IL21R immunodeficiency
MedGen UID:
767601
Concept ID:
C3554687
Disease or Syndrome
Immunodeficiency-56 is an autosomal recessive primary immunodeficiency characterized by B- and T-cell defects and variable dysfunction of NK cells. Patients tend to have normal numbers of lymphocytes, but show defective class-switched B cells, low IgG, defective antibody response, and defective T-cell responses to certain antigens (summary by Kotlarz et al., 2013).
Short-rib thoracic dysplasia 10 with or without polydactyly
MedGen UID:
816505
Concept ID:
C3810175
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).
Spinocerebellar ataxia, autosomal recessive 21
MedGen UID:
895546
Concept ID:
C4225236
Disease or Syndrome
Autosomal recessive spinocerebellar ataxia-21 is a neurologic disorder characterized by onset of cerebellar ataxia associated with cerebellar atrophy in early childhood. Affected individuals also have recurrent episodes of liver failure in the first decade, resulting in chronic liver fibrosis, as well as later onset of a peripheral neuropathy. Mild learning disabilities may also occur (summary by Schmidt et al., 2015).
Bile acid synthesis defect, congenital, 5
MedGen UID:
904751
Concept ID:
C4225390
Congenital Abnormality
Cholestasis, progressive familial intrahepatic, 5
MedGen UID:
934714
Concept ID:
C4310747
Disease or Syndrome
Progressive familial intrahepatic cholestasis-5 (PFIC5) is an autosomal recessive severe liver disorder characterized by onset of intralobular cholestasis in the neonatal period. The disease is rapidly progressive, leading to liver failure and death if liver transplant is not performed. Other features include abnormal liver enzymes, low to normal gamma-glutamyl transferase (GGT) activity, increased alpha-fetoprotein, and a vitamin K-independent coagulopathy (summary by Gomez-Ospina et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of PFIC, see PFIC1 (211600).
Gilbert syndrome
MedGen UID:
4891
Concept ID:
C0017551
Disease or Syndrome
The hereditary hyperbilirubinemias (Wolkoff et al., 1983) include (1) those resulting in predominantly unconjugated hyperbilirubinemia: Gilbert or Arias syndrome, Crigler-Najjar syndrome type I (218800), and Crigler-Najjar syndrome type II (606785); and (2) those resulting in predominantly conjugated hyperbilirubinemia: Dubin-Johnson syndrome (237500), Rotor syndrome (237450), and several forms of intrahepatic cholestasis (147480, 211600, 214950, 243300). Detailed studies show that patients with Gilbert syndrome have reduced activity of bilirubin glucuronosyltransferase (Bosma et al., 1995, Koiwai et al., 1995). Genetic Heterogeneity of Hyperbilirubinemia See also Crigler-Najjar syndrome type I (HBLRCN1; 218800), Crigler-Najjar syndrome type II (HBLRCN2; 606785), and transient familial neonatal hyperbilirubinemia (HBLRTFN; 237900), all caused by mutation in the UGT1A1 gene (191740) on chromosome 2q37; Dubin-Johnson syndrome (DJS, HBLRDJ; 237500), caused by mutation in the ABCC2 gene (601107) on chromosome 10q24; and Rotor syndrome (HBLRR; 237450), caused by digenic mutation in the SLCO1B1 (604843) and SLCOB3 (605495) genes, both on chromosome 12p.

Recent clinical studies

Etiology

Kurokohchi K, Imataki O, Kubo F
World J Gastroenterol 2015 Jul 14;21(26):8203-7. doi: 10.3748/wjg.v21.i26.8203. PMID: 26185395Free PMC Article
Weymann A, Patil NP, Sabashnikov A, Mohite PN, Garcia Saez D, Bireta C, Wahlers T, Karck M, Kallenbach K, Ruhparwar A, Fatullayev J, Amrani M, De Robertis F, Bahrami T, Popov AF, Simon AR
Artif Organs 2015 Apr;39(4):336-42. Epub 2014 Oct 27 doi: 10.1111/aor.12375. PMID: 25345547
Tanaka S, Iimuro Y, Hirano T, Hai S, Suzumura K, Fujimoto J
Hepatogastroenterology 2014 May;61(131):755-61. PMID: 26176070
Camkıran A, Araz C, Seyhan Ballı S, Torgay A, Moray G, Pirat A, Arslan G, Haberal M
Exp Clin Transplant 2014 Mar;12 Suppl 1:106-9. PMID: 24635805
Öztürk Y, Berktaş S, Soylu ÖB, Karademır S, Astarcioğlu H, Arslan N, Astarcioğlu İ
Turk J Gastroenterol 2010 Sep;21(3):270-4. PMID: 20931431

Diagnosis

Sinha R, Chapman AR, Reid GT, Hayes PC
J R Coll Physicians Edinb 2015;45(2):136-40. doi: 10.4997/JRCPE.2015.210. PMID: 26181530
Weymann A, Patil NP, Sabashnikov A, Mohite PN, Garcia Saez D, Bireta C, Wahlers T, Karck M, Kallenbach K, Ruhparwar A, Fatullayev J, Amrani M, De Robertis F, Bahrami T, Popov AF, Simon AR
Artif Organs 2015 Apr;39(4):336-42. Epub 2014 Oct 27 doi: 10.1111/aor.12375. PMID: 25345547
Tanaka S, Iimuro Y, Hirano T, Hai S, Suzumura K, Fujimoto J
Hepatogastroenterology 2014 May;61(131):755-61. PMID: 26176070
Camkıran A, Araz C, Seyhan Ballı S, Torgay A, Moray G, Pirat A, Arslan G, Haberal M
Exp Clin Transplant 2014 Mar;12 Suppl 1:106-9. PMID: 24635805
Öztürk Y, Berktaş S, Soylu ÖB, Karademır S, Astarcioğlu H, Arslan N, Astarcioğlu İ
Turk J Gastroenterol 2010 Sep;21(3):270-4. PMID: 20931431

Therapy

Lunsford KE, Bodzin AS, Reino DC, Wang HL, Busuttil RW
World J Gastroenterol 2016 Dec 7;22(45):10071-10076. doi: 10.3748/wjg.v22.i45.10071. PMID: 28018115Free PMC Article
Kurokohchi K, Imataki O, Kubo F
World J Gastroenterol 2015 Jul 14;21(26):8203-7. doi: 10.3748/wjg.v21.i26.8203. PMID: 26185395Free PMC Article
Sinha R, Chapman AR, Reid GT, Hayes PC
J R Coll Physicians Edinb 2015;45(2):136-40. doi: 10.4997/JRCPE.2015.210. PMID: 26181530
Tanaka S, Iimuro Y, Hirano T, Hai S, Suzumura K, Fujimoto J
Hepatogastroenterology 2014 May;61(131):755-61. PMID: 26176070
Camkıran A, Araz C, Seyhan Ballı S, Torgay A, Moray G, Pirat A, Arslan G, Haberal M
Exp Clin Transplant 2014 Mar;12 Suppl 1:106-9. PMID: 24635805

Prognosis

Varma H, Faust PL, Iglesias AD, Lagana SM, Wou K, Hirano M, DiMauro S, Mansukani MM, Hoff KE, Nagy PL, Copeland WC, Naini AB
Eur J Med Genet 2016 Oct;59(10):540-5. Epub 2016 Aug 31 doi: 10.1016/j.ejmg.2016.08.012. PMID: 27592148Free PMC Article
Weymann A, Patil NP, Sabashnikov A, Mohite PN, Garcia Saez D, Bireta C, Wahlers T, Karck M, Kallenbach K, Ruhparwar A, Fatullayev J, Amrani M, De Robertis F, Bahrami T, Popov AF, Simon AR
Artif Organs 2015 Apr;39(4):336-42. Epub 2014 Oct 27 doi: 10.1111/aor.12375. PMID: 25345547
Tanaka S, Iimuro Y, Hirano T, Hai S, Suzumura K, Fujimoto J
Hepatogastroenterology 2014 May;61(131):755-61. PMID: 26176070
Camkıran A, Araz C, Seyhan Ballı S, Torgay A, Moray G, Pirat A, Arslan G, Haberal M
Exp Clin Transplant 2014 Mar;12 Suppl 1:106-9. PMID: 24635805
Öztürk Y, Berktaş S, Soylu ÖB, Karademır S, Astarcioğlu H, Arslan N, Astarcioğlu İ
Turk J Gastroenterol 2010 Sep;21(3):270-4. PMID: 20931431

Clinical prediction guides

Varma H, Faust PL, Iglesias AD, Lagana SM, Wou K, Hirano M, DiMauro S, Mansukani MM, Hoff KE, Nagy PL, Copeland WC, Naini AB
Eur J Med Genet 2016 Oct;59(10):540-5. Epub 2016 Aug 31 doi: 10.1016/j.ejmg.2016.08.012. PMID: 27592148Free PMC Article
Sinha R, Chapman AR, Reid GT, Hayes PC
J R Coll Physicians Edinb 2015;45(2):136-40. doi: 10.4997/JRCPE.2015.210. PMID: 26181530
Weymann A, Patil NP, Sabashnikov A, Mohite PN, Garcia Saez D, Bireta C, Wahlers T, Karck M, Kallenbach K, Ruhparwar A, Fatullayev J, Amrani M, De Robertis F, Bahrami T, Popov AF, Simon AR
Artif Organs 2015 Apr;39(4):336-42. Epub 2014 Oct 27 doi: 10.1111/aor.12375. PMID: 25345547
Tanaka S, Iimuro Y, Hirano T, Hai S, Suzumura K, Fujimoto J
Hepatogastroenterology 2014 May;61(131):755-61. PMID: 26176070
Camkıran A, Araz C, Seyhan Ballı S, Torgay A, Moray G, Pirat A, Arslan G, Haberal M
Exp Clin Transplant 2014 Mar;12 Suppl 1:106-9. PMID: 24635805

Recent systematic reviews

Maitta RW, Choate J, Emre SH, Luczycki SM, Wu Y
J Clin Apher 2012;27(6):320-9. Epub 2012 Jul 26 doi: 10.1002/jca.21244. PMID: 22833397
Gasco J, Rangel-Castilla L, Franklin B, Thomas PG, Patterson JT
Acta Neurochir Suppl 2010;106:311-4. doi: 10.1007/978-3-211-98811-4_58. PMID: 19812970
Han MK, Hyzy R
Crit Care Med 2006 Sep;34(9 Suppl):S225-31. doi: 10.1097/01.CCM.0000231882.85350.71. PMID: 16917427
Tissières P, Sasbón JS, Devictor D
Pediatr Crit Care Med 2005 Sep;6(5):585-91. PMID: 16148822
Rahman T, Hodgson H
Intensive Care Med 2001 Mar;27(3):467-76. PMID: 11355114

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