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Lactic acidosis

MedGen UID:
344523
Concept ID:
C1855560
Finding
Synonyms: Hyperlacticacidemia; Lactic acidemia; Lacticacidemia; Lacticacidosis
 
HPO: HP:0003128

Conditions with this feature

Hereditary fructosuria
MedGen UID:
42105
Concept ID:
C0016751
Disease or Syndrome
Fructose intolerance becomes apparent in infancy at the time of weaning, when fructose or sucrose is added to the diet. Clinical features include recurrent vomiting, abdominal pain, and hypoglycemia that may be fatal. Long-term exposure to fructose can result in liver failure, renal tubulopathy, and growth retardation. Older patients who survive infancy develop a natural avoidance of sweets and fruits. Ali et al. (1998) provided a detailed review of the biochemical, genetic, and molecular basis of aldolase B deficiency in hereditary fructose intolerance.
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.
Kearns Sayre syndrome
MedGen UID:
9618
Concept ID:
C0022541
Disease or Syndrome
A mitochondrial disorder featuring the triad of chronic progressive EXTERNAL OPHTHALMOPLEGIA, cardiomyopathy (CARDIOMYOPATHIES) with conduction block (HEART BLOCK), and RETINITIS PIGMENTOSA. Disease onset is in the first or second decade. Elevated CSF protein, sensorineural deafness, seizures, and pyramidal signs may also be present. Ragged-red fibers are found on muscle biopsy. (Adams et al., Principles of Neurology, 6th ed, p984)
Leigh's disease
MedGen UID:
44095
Concept ID:
C0023264
Disease or Syndrome
Leigh syndrome is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. The lesions are areas of demyelination, gliosis, necrosis, spongiosis, or capillary proliferation. Clinical symptoms depend on which areas of the central nervous system are involved. The most common underlying cause is a defect in oxidative phosphorylation (Dahl, 1998). Leigh syndrome may be a feature of a deficiency of any of the mitochondrial respiratory chain complexes: complex I deficiency (252010), complex II deficiency (252011), complex III deficiency (124000), complex IV deficiency (cytochrome c oxidase; 220110), or complex V deficiency (604273).
Maple syrup urine disease
MedGen UID:
6217
Concept ID:
C0024776
Disease or Syndrome
Maple syrup urine disease (MSUD) is classified as classic or intermediate. Twelve hours after birth, untreated neonates with classic MSUD have a maple syrup odor in cerumen; by 12-24 hours, elevated plasma concentrations of branched-chain amino acids (BCAAs) (leucine, isoleucine, and valine) and allo-isoleucine, as well as a generalized disturbance of plasma amino acid concentration ratios; by age two to three days, ketonuria, irritability, and poor feeding; by age four to five days, deepening encephalopathy manifesting as lethargy, intermittent apnea, opisthotonus, and stereotyped movements such as "fencing" and "bicycling." By age seven to ten days, coma and central respiratory failure may supervene. Individuals with intermediate MSUD have partial BCKAD enzyme deficiency that only manifests intermittently or responds to dietary thiamine therapy; these individuals can experience severe metabolic intoxication and encephalopathy during sufficient catabolic stress.
Pyruvate carboxylase deficiency
MedGen UID:
18801
Concept ID:
C0034341
Disease or Syndrome
Pyruvate carboxylase (PC) deficiency is characterized in most affected individuals by failure to thrive, developmental delay, recurrent seizures, and metabolic acidosis. Three clinical types are recognized: type A (infantile form), in which most affected children die in infancy or early childhood; type B (severe neonatal form), in which affected infants have hepatomegaly, pyramidal tract signs, and abnormal movement and die within the first three months of life; and type C (intermittent/benign form), in which affected individuals have normal or mildly delayed neurologic development and episodic metabolic acidosis.
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).
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.
Deficiency of cytochrome-b5 reductase
MedGen UID:
75661
Concept ID:
C0268193
Disease or Syndrome
Methemoglobinemia due to NADH-cytochrome b5 reductase deficiency is an autosomal recessive disorder characterized clinically by decreased oxygen carrying capacity of the blood, with resultant cyanosis and hypoxia (review by Percy and Lappin, 2008). There are 2 types of methemoglobin reductase deficiency. In type I, the defect affects the soluble form of the enzyme, is restricted to red blood cells, and causes well-tolerated methemoglobinemia. In type II, the defect affects both the soluble and microsomal forms of the enzyme and is thus generalized, affecting red cells, leukocytes, and all body tissues. Type II methemoglobinemia is associated with mental deficiency and other neurologic symptoms. The neurologic symptoms may be related to the major role played by the cytochrome b5 system in the desaturation of fatty acids (Vives-Corrons et al., 1978; Kaplan et al., 1979).
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.
Propionic acidemia
MedGen UID:
75694
Concept ID:
C0268579
Disease or Syndrome
The spectrum of propionic acidemia (PA) ranges from neonatal-onset to late-onset disease. Neonatal-onset PA, the most common form, is characterized by poor feeding, vomiting, and somnolence in the first days of life in a previously healthy infant, followed by lethargy, seizures, coma, and death. It is frequently accompanied by metabolic acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenias. Late-onset PA includes developmental regression, chronic vomiting, protein intolerance, failure to thrive, hypotonia, and occasionally basal ganglia infarction (resulting in dystonia and choreoathetosis) and cardiomyopathy. Affected children can have an acute decompensation that resembles the neonatal presentation and is precipitated by a catabolic stress such as infection, injury, or surgery. Isolated cardiomyopathy and arrhythmia can be observed on rare occasion in the absence of clinical metabolic decompensation or neurocognitive deficits. Manifestations of neonatal and late-onset PA over time can include growth impairment, intellectual disability, seizures, basal ganglia lesions, pancreatitis, and cardiomyopathy. Other rarely reported complications include optic atrophy, hearing loss, premature ovarian insufficiency (POI), and chronic renal failure.
3-Hydroxyisobutyric aciduria
MedGen UID:
90996
Concept ID:
C0342737
Disease or Syndrome
Phosphate transport defect
MedGen UID:
87455
Concept ID:
C0342749
Disease or Syndrome
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.
Pearson's syndrome
MedGen UID:
90997
Concept ID:
C0342773
Disease or Syndrome
Mitochondrial DNA (mtDNA) deletion syndromes predominantly comprise three overlapping phenotypes that are usually simplex (i.e., a single occurrence in a family), but rarely may be observed in different members of the same family or may evolve in a given individual over time. The three phenotypes are Kearns-Sayre syndrome (KSS), Pearson syndrome, and progressive external ophthalmoplegia (PEO). Rarely Leigh syndrome can be a manifestation of a mtDNA deletion. KSS is a multisystem disorder defined by the triad of onset before age 20 years, pigmentary retinopathy, and PEO. In addition, affected individuals have at least one of the following: cardiac conduction block, cerebrospinal fluid protein concentration greater than 100 mg/dL, or cerebellar ataxia. Onset is usually in childhood. Pearson syndrome is characterized by sideroblastic anemia and exocrine pancreas dysfunction and is usually fatal in infancy. PEO, characterized by ptosis, paralysis of the extraocular muscles (ophthalmoplegia), oropharyngeal weakness, and variably severe proximal limb weakness, is relatively benign.
Mitochondrial trifunctional protein deficiency
MedGen UID:
87460
Concept ID:
C0342786
Disease or Syndrome
The mitochondrial trifunctional protein, composed of 4 alpha and 4 beta subunits, catalyzes 3 steps in mitochondrial beta-oxidation of fatty acids: long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), long-chain enoyl-CoA hydratase, and long-chain thiolase activities. Trifunctional protein deficiency is characterized by decreased activity of all 3 enzymes. Clinically, classic trifunctional protein deficiency can be classified into 3 main clinical phenotypes: neonatal onset of a severe, lethal condition resulting in sudden unexplained infant death (SIDS; 272120), infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy (Spiekerkoetter et al., 2003). Some patients with MTP deficiency show a protracted progressive course associated with myopathy, recurrent rhabdomyolysis, and sensorimotor axonal neuropathy. These patients tend to survive into adolescence and adulthood (den Boer et al., 2003). See also isolated LCHAD deficiency (609016), which is caused by mutation in the HADHA gene.
Deficiency of malonyl-CoA decarboxylase
MedGen UID:
91001
Concept ID:
C0342793
Disease or Syndrome
Malonyl-CoA decarboxylase deficiency is an uncommon inherited metabolic disease. The characteristic phenotype is variable, but may include developmental delay in early childhood, seizures, hypotonia, diarrhea, vomiting, metabolic acidosis, hypoglycemia, ketosis, abnormal urinary compounds, lactic acidemia, and hypertrophic cardiomyopathy (Sweetman and Williams, 2001).
Central sleep apnea syndrome
MedGen UID:
99249
Concept ID:
C0520680
Disease or Syndrome
A condition associated with multiple episodes of sleep apnea which are distinguished from obstructive sleep apnea (SLEEP APNEA, OBSTRUCTIVE) by the complete cessation of efforts to breathe. This disorder is associated with dysfunction of central nervous system centers that regulate respiration.
Myoneural gastrointestinal encephalopathy syndrome
MedGen UID:
167876
Concept ID:
C0872218
Disease or Syndrome
Mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease is characterized by progressive gastrointestinal dysmotility and cachexia manifesting as early satiety, nausea, dysphagia, gastroesophageal reflux, postprandial emesis, episodic abdominal pain and/or distention, and diarrhea; ptosis/ophthalmoplegia or ophthalmoparesis; hearing loss; and demyelinating peripheral neuropathy manifesting as paresthesias (tingling, numbness, and pain) and symmetric and distal weakness more prominently affecting the lower extremities. The order in which manifestations appear is unpredictable. Onset is usually between the first and fifth decades; in about 60% of individuals, symptoms begin before age 20 years.
MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 2
MedGen UID:
371986
Concept ID:
C1835161
Finding
Mitochondrial phosphate carrier deficiency
MedGen UID:
324373
Concept ID:
C1835845
Disease or Syndrome
Pyruvate dehydrogenase phosphatase deficiency
MedGen UID:
332448
Concept ID:
C1837429
Disease or Syndrome
Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking. Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood.
Myopathy, lactic acidosis, and sideroblastic anemia 1
MedGen UID:
373888
Concept ID:
C1838103
Disease or Syndrome
Myopathy, lactic acidosis, and sideroblastic anemia (MLASA) is a rare autosomal recessive oxidative phosphorylation disorder specific to skeletal muscle and bone marrow (Bykhovskaya et al., 2004). Genetic Heterogeneity of MLASA MLASA2 (613561) is caused by homozygous mutation in the YARS2 gene (610957) on chromosome 12p.11.21.
Succinic acidemia
MedGen UID:
373921
Concept ID:
C1838243
Disease or Syndrome
Mitochondrial myopathy, lethal, infantile
MedGen UID:
374077
Concept ID:
C1838876
Disease or Syndrome
Mitochondrial diseases are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain. They can be caused by mutation of genes encoded by either nuclear DNA or mitochondrial DNA (mtDNA). While some mitochondrial disorders only affect a single organ (e.g., the eye in Leber hereditary optic neuropathy [LHON]), many involve multiple organ systems and often present with prominent neurologic and myopathic features. Mitochondrial disorders may present at any age. Many individuals with a mutation of mtDNA display a cluster of clinical features that fall into a discrete clinical syndrome, such as the Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy with ragged-red fibers (MERRF), neurogenic weakness with ataxia and retinitis pigmentosa (NARP), or Leigh syndrome (LS). However, considerable clinical variability exists and many individuals do not fit neatly into one particular category, which is well-illustrated by the overlapping spectrum of disease phenotypes (including mitochondrial recessive ataxia syndrome (MIRAS) resulting from mutation of the nuclear gene POLG, which has emerged as a major cause of mitochondrial disease. Common clinical features of mitochondrial disease – whether involving a mitochondrial or nuclear gene – include ptosis, external ophthalmoplegia, proximal myopathy and exercise intolerance, cardiomyopathy, sensorineural deafness, optic atrophy, pigmentary retinopathy, and diabetes mellitus. Common central nervous system findings are fluctuating encephalopathy, seizures, dementia, migraine, stroke-like episodes, ataxia, and spasticity. A high incidence of mid- and late pregnancy loss is a common occurrence that often goes unrecognized.
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 B17.2L (609653), HRPAP20 (611776), C20ORF7 (612360), NUBPL (613621), and NDUFAF1 (606934). 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 gene (300078). 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).
Leigh Syndrome, X-Linked
MedGen UID:
326602
Concept ID:
C1839885
Disease or Syndrome
Leigh syndrome is a severe neurological disorder that typically arises in the first year of life. This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within a couple of years, usually due to respiratory failure. A small number of individuals develop symptoms in adulthood or have symptoms that worsen more slowly. The first signs of Leigh syndrome seen in infancy are usually vomiting, diarrhea, and difficulty swallowing (dysphagia) that leads to eating problems. These problems often result in an inability to grow and gain weight at the expected rate (failure to thrive). Severe muscle and movement problems are common in Leigh syndrome. Affected individuals may develop weak muscle tone (hypotonia), involuntary muscle contractions (dystonia), and problems with movement and balance (ataxia). Loss of sensation and weakness in the limbs (peripheral neuropathy), common in people with Leigh syndrome, may also make movement difficult. Several other features may occur in people with Leigh syndrome. Many affected individuals develop weakness or paralysis of the muscles that move the eyes (ophthalmoparesis); rapid, involuntary eye movements (nystagmus); or degeneration of the nerves that carry information from the eyes to the brain (optic atrophy). Severe breathing problems are common in people with Leigh syndrome, and these problems can worsen until they cause acute respiratory failure. Some affected individuals develop hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood. In addition, a substance called lactate can build up in the body, and excessive amounts are often found in the blood, cerebrospinal fluid, or urine of people with Leigh syndrome. The signs and symptoms of Leigh syndrome are caused in part by patches of damaged tissue (lesions) that develop in the brains of people with this condition. A procedure called magnetic resonance imaging (MRI) reveals characteristic lesions in certain regions of the brain and the brainstem (the part of the brain that is connected to the spinal cord). These regions include the basal ganglia, which help control movement; the cerebellum, which controls the ability to balance and coordinates movement; and the brainstem, which controls functions such as swallowing, breathing, hearing, and seeing. The brain lesions are often accompanied by loss of the myelin coating around nerves (demyelination), which reduces the ability of the nerves to activate muscles used for movement or relay sensory information back to the brain.
Coenzyme Q10 deficiency
MedGen UID:
334528
Concept ID:
C1843920
Disease or Syndrome
Primary CoQ10 deficiency is a rare, clinically heterogeneous autosomal recessive disorder caused by mutation in any of the genes encoding proteins directly involved in the synthesis of coenzyme Q (review by Quinzii and Hirano, 2011). Coenzyme Q10 (CoQ10), or ubiquinone, is a mobile lipophilic electron carrier critical for electron transfer by the mitochondrial inner membrane respiratory chain (Duncan et al., 2009). The disorder has been associated with 5 major phenotypes, but the molecular basis has not been determined in most patients with the disorder and there are no clear genotype/phenotype correlations. The phenotypes include an encephalomyopathic form with seizures and ataxia (Ogasahara et al., 1989); a multisystem infantile form with encephalopathy, cardiomyopathy and renal failure (Rotig et al., 2000); a predominantly cerebellar form with ataxia and cerebellar atrophy (Lamperti et al., 2003); Leigh syndrome with growth retardation (van Maldergem et al., 2002); and an isolated myopathic form (Lalani et al., 2005). The correct diagnosis is important because some patients may show a favorable response to CoQ10 treatment. Genetic Heterogeneity of Primary Coenzyme Q10 Deficiency See also COQ10D2 (614651), caused by mutation in the PDSS1 gene (607429) on chromosome 10p12; COQ10D3 (614652), caused by mutation in the PDSS2 gene (610564) on chromosome 6q21; COQ10D4 (612016), caused by mutation in the COQ8 gene (ADCK3; 606980) on chromosome 1q42; COQ10D5 (614654), caused by mutation in the COQ9 gene (612837) on chromosome 16q21; and COQ10D6 (614650), caused by mutation in the COQ6 gene (614647) on chromosome 14q24. A single patient with primary CoQ10 deficiency associated with a de novo heterozygous 3.9-Mb deletion on chromosome 9q34 has been reported; the deleted region included at least 80 genes, 1 of which was COQ4 (612898) (Salviati et al., 2012). Secondary CoQ10 deficiency has been reported in association with glutaric aciduria type IIC (MADD; 231680), caused by mutation in the ETFDH gene (231675) on chromosome 4q, and with ataxia-oculomotor apraxia syndrome-1 (AOA1; 208920), caused by mutation in the APTX gene (606350) on chromosome 9p13.
2-methyl-3-hydroxybutyric aciduria
MedGen UID:
336957
Concept ID:
C1845517
Disease or Syndrome
HSD10 deficiency is an X-linked dominant neurodegenerative disorder characterized by onset in late infancy or during childhood. The severity is highly variable, but some patients have slow loss of developmental skills, cardiomyopathy, retinal degeneration, and seizures; the features resemble a mitochondrial disorder. Unlike other organic acidurias, most patients do not develop severe metabolic crises in the neonatal period (summary by Rauschenberger et al., 2010).
Amish lethal microcephaly
MedGen UID:
375938
Concept ID:
C1846648
Disease or Syndrome
Amish lethal microcephaly is characterized by microcephaly and early death. The occipitofrontal circumference is typically six to 12 standard deviations below the mean; anterior and posterior fontanels are closed at birth and facial features are distorted. The average life span is between five and six months.
Hypotonia-cystinuria syndrome
MedGen UID:
341133
Concept ID:
C1848030
Disease or Syndrome
Phenformin 4-hydroxylation
MedGen UID:
342365
Concept ID:
C1849927
Molecular Function
Navajo neurohepatopathy
MedGen UID:
338045
Concept ID:
C1850406
Disease or Syndrome
MPV17-related hepatocerebral mitochondrial DNA (mtDNA) depletion syndrome is characterized by infantile-onset liver dysfunction that typically progresses to liver failure; neurologic involvement (developmental delay, hypotonia, and muscle weakness in the majority; ataxia, seizures, and motor and sensory peripheral neuropathy in some); failure to thrive; and metabolic derangements including lactic acidosis and hypoglycemic crises. Less frequent manifestations include renal tubulopathy, hypoparathyroidism, gastrointestinal dysmotility, and corneal anesthesia. Progressive liver disease often leads to death in infancy or early childhood. Hepatocellular carcinoma has been reported.
Myopathy with lactic acidosis, hereditary
MedGen UID:
342573
Concept ID:
C1850718
Disease or Syndrome
Myopathy with deficiency of ISCU, a mitochondrial myopathy, is characterized by lifelong exercise intolerance in which minor exertion causes tachycardia, shortness of breath, and fatigue and pain of active muscles; episodes of more profound exercise intolerance associated with rhabdomyolysis, myoglobinuria, and weakness that may be severe; and typically full recovery of muscle strength between episodes of rhabdomyolysis. Affected individuals usually have near-normal strength; they can have large calves.
Mitochondrial complex III deficiency
MedGen UID:
377658
Concept ID:
C1852372
Disease or Syndrome
Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia, failure to thrive, encephalopathy, and delayed psychomotor development. Visceral involvement, including hepatopathy and renal tubulopathy, may also occur. Many patients die in early childhood, but some may show longer survival (de Lonlay et al., 2001; De Meirleir et al., 2003). Genetic Heterogeneity of Mitochondrial Complex III Deficiency Mitochondrial complex III deficiency can be caused by mutation in several different nuclear-encoded genes. See MC3DN2 (615157), caused by mutation in the TTC19 gene (613814) on chromosome 17p12; MC3DN3 (615158), caused by mutation in the UQCRB gene (191330) on chromosome 8q; MC3DN4 (615159), caused by mutation in the UQCRQ gene (612080) on chromosome 5q31; MC3DN5 (615160), caused by mutation in the UQCRC2 gene (191329) on chromosome 16p12; MC3DN6 (615453), caused by mutation in the CYC1 gene (123980) on chromosome 8q24; MC3DN7 (615824), caused by mutation in the UQCC2 gene (614461) on chromosome 6p21; MC3DN8 (615838), caused by mutation in the LYRM7 gene (615831) on chromosome 5q23; and MC3DN9 (616111), caused by mutation in the UQCC3 gene (616097) on chromosome 11q12. See also MTYCB (516020) for a discussion of a milder phenotype associated with isolated mitochondrial complex III deficiency and mutations in a mitochondrial-encoded gene.
Multiple mitochondrial dysfunctions syndrome 1
MedGen UID:
343044
Concept ID:
C1854052
Disease or Syndrome
Multiple mitochondrial dysfunctions syndrome is a severe autosomal recessive disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, and early death (summary by Seyda et al., 2001). Genetic Heterogeneity of Multiple Mitochondrial Dysfunctions Syndrome See also MMDS2 (614299), caused by mutation in the BOLA3 gene (613183) on chromosome 2p13; and MMDS3 (615330), caused by mutation in the IBA57 gene (615316) on chromosome 1q42.
Mitochondrial myopathy with lactic acidosis
MedGen UID:
343245
Concept ID:
C1855033
Disease or Syndrome
Pyruvate dehydrogenase E3-binding protein deficiency
MedGen UID:
343383
Concept ID:
C1855553
Disease or Syndrome
Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking. Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood.
Pyruvate dehydrogenase E2 deficiency
MedGen UID:
343386
Concept ID:
C1855565
Disease or Syndrome
Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking. Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood.
Leigh syndrome, French Canadian type
MedGen UID:
387801
Concept ID:
C1857355
Disease or Syndrome
The French Canadian type of Leigh syndrome is an autosomal recessive severe neurologic disorder with onset in infancy. Features include delayed psychomotor development, mental retardation, mild dysmorphic facial features, hypotonia, ataxia, and the development of lesions in the brainstem and basal ganglia. Affected individuals tend to have episodic metabolic and/or neurologic crises in early childhood, which often lead to early death (summary by Debray et al., 2011). For a phenotypic description and a discussion of genetic heterogeneity of Leigh syndrome, see 256000.
Combined oxidative phosphorylation deficiency 4
MedGen UID:
387884
Concept ID:
C1857682
Disease or Syndrome
Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency
MedGen UID:
346817
Concept ID:
C1858424
Disease or Syndrome
Cytochrome c oxidase deficiency is a genetic condition that can affect several parts of the body, including the muscles used for movement (skeletal muscles), the heart, the brain, or the liver. Signs and symptoms of cytochrome c oxidase deficiency usually begin before age 2 but can appear later in mildly affected individuals. The severity of cytochrome c oxidase deficiency varies widely among affected individuals, even among those in the same family. People who are mildly affected tend to have muscle weakness (myopathy) and poor muscle tone (hypotonia) with no other health problems. More severely affected people have myopathy along with severe brain dysfunction (encephalomyopathy). Approximately one quarter of individuals with cytochrome c oxidase deficiency have a type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). Another possible feature of this condition is an enlarged liver, which may lead to liver failure. Most individuals with cytochrome c oxidase deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can cause nausea and an irregular heart rate, and can be life-threatening. Many people with cytochrome c oxidase deficiency have a specific group of features known as Leigh syndrome. The signs and symptoms of Leigh syndrome include loss of mental function, movement problems, hypertrophic cardiomyopathy, eating difficulties, and brain abnormalities. Cytochrome c oxidase deficiency is one of the many causes of Leigh syndrome. Cytochrome c oxidase deficiency is frequently fatal in childhood, although some individuals with mild signs and symptoms survive into adolescence or adulthood.
Alaninuria with microcephaly, dwarfism, enamel hypoplasia and diabetes mellitus
MedGen UID:
348505
Concept ID:
C1859965
Disease or Syndrome
Combined oxidative phosphorylation deficiency 3
MedGen UID:
355842
Concept ID:
C1864840
Disease or Syndrome
Combined oxidative phosphorylation deficiency 2
MedGen UID:
400626
Concept ID:
C1864843
Disease or Syndrome
Ethylmalonic encephalopathy
MedGen UID:
355966
Concept ID:
C1865349
Disease or Syndrome
Ethylmalonic encephalopathy is an autosomal recessive severe metabolic disorder of infancy affecting the brain, gastrointestinal tract, and peripheral vessels. The disorder is characterized by neurodevelopmental delay and regression, prominent pyramidal and extrapyramidal signs, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhea. Brain MRI shows necrotic lesions in deep gray matter structures. Death usually occurs in the first decade of life (summary by Drousiotou et al., 2011).
Pyruvate dehydrogenase E1-beta deficiency
MedGen UID:
357977
Concept ID:
C1867399
Disease or Syndrome
Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking. Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood.
Acyl-CoA dehydrogenase family, member 9, deficiency of
MedGen UID:
370195
Concept ID:
C1970173
Disease or Syndrome
ACAD9 deficiency is an autosomal recessive multisystemic 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.
Spinocerebellar ataxia, autosomal recessive 9
MedGen UID:
436985
Concept ID:
C2677589
Disease or Syndrome
Primary coenzyme Q10 deficiency-4 is an autosomal recessive disorder characterized by childhood-onset of cerebellar ataxia and exercise intolerance. Some affected individuals develop seizures and have mild mental impairment, indicating variable severity. Oral coenzyme Q10 supplementation does not result in significant improvement of neurologic symptoms (summary by Mollet et al., 2008 and Lagier-Tourenne et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of primary coenzyme Q10 deficiency, see COQ10D1 (607426).
Nuclearly-encoded mitochondrial complex V (ATP synthase) deficiency 1
MedGen UID:
398105
Concept ID:
C2700431
Disease or Syndrome
A distinct group of inborn defects of complex V (ATP synthase) is represented by the enzyme deficiency due to nuclear genome mutations characterized by a selective inhibition of ATP synthase biogenesis. Biochemically, the patients show a generalized decrease in the content of ATP synthase complex which is less than 30% of normal. Most cases present with neonatal-onset hypotonia, lactic acidosis, hyperammonemia, hypertrophic cardiomyopathy, and 3-methylglutaconic aciduria. Many patients die within a few months or years (summary by Mayr et al., 2010). Genetic Heterogeneity of Mitochondrial Complex V Deficiency Other nuclear types of mitochondrial complex V deficiency include MC5DN2 (614052), caused by mutation in the TMEM70 gene (612418) on chromosome 8q21; MC5DN3 (614053), caused by mutation in the ATP5E gene (606153) on chromosome 20q13; and MC5DN4 (615228), caused by mutation in the ATP5A1 gene (164360) on chromosome 18q. Mutations in the mitochondrial-encoded MTATP6 (516060) and MTATP8 (516070) genes can also cause mitochondrial complex V deficiency (see, e.g., 551500 and 500003).
Mitochondrial DNA depletion syndrome, encephalomyopathic form, with renal tubulopathy
MedGen UID:
412815
Concept ID:
C2749861
Disease or Syndrome
Mitochondrial DNA depletion syndrome-8A is a severe autosomal recessive disorder characterized by neonatal hypotonia, lactic acidosis, and neurologic deterioration. Renal tubular involvement may also occur (Bourdon et al., 2007). Mitochondrial DNA depletion syndrome-8B is characterized by ophthalmoplegia, ptosis, gastrointestinal dysmotility, cachexia, peripheral neuropathy, and brain MRI changes, known as the MNGIE phenotype (Shaibani et al., 2009). For a discussion of genetic heterogeneity of mtDNA depletion syndromes, see MTDPS1 (603041).
Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria)
MedGen UID:
413170
Concept ID:
C2749864
Disease or Syndrome
SUCLA2-related mitochondrial DNA (mtDNA) depletion syndrome is characterized by onset of severe hypotonia in early infancy (birth to five months); severe muscular atrophy with failure to achieve independent ambulation; progressive scoliosis or kyphosis; dystonia and/or hyperkinesias (i.e., athetoid or choreiform movements); epilepsy (infantile spasms or generalized convulsions with onset from birth to three years) in a few children; postnatal growth retardation; and severe sensorineural hearing impairment. The outcome is poor with early lethality.
Liver failure acute infantile
MedGen UID:
414410
Concept ID:
C2751567
Disease or Syndrome
Acute infantile liver failure resulting from TRMU mutation is a transient disorder of hepatic function. In addition to elevated liver enzymes, jaundice, vomiting, coagulopathy, and hyperbilirubinemia, the presence of increased serum lactate is consistent with a defect in mitochondrial respiratory function. With supportive care, patients who survive the initial acute episode can recover and show normal development (Zeharia et al., 2009). See also transient infantile mitochondrial myopathy (MMIT; 500009), which is a similar disorder. A more severe, permanent disorder with some overlapping features is associated with mitochondrial DNA depletion (251880). See ILFS1 (615438) for information on syndromic infantile liver failure.
Glycogen storage disease IXc
MedGen UID:
442778
Concept ID:
C2751643
Disease or Syndrome
Glycogen storage disease IXc is characterized by onset in childhood of hepatomegaly, hypotonia, growth retardation in childhood, and liver dysfunction. These symptoms improve with age in most cases; however, some patients may develop hepatic fibrosis or cirrhosis (Burwinkel et al., 1998).
Malignant hyperthermia susceptibility type 3
MedGen UID:
418956
Concept ID:
C2930982
Pathologic Function
Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain volatile anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with a depolarizing muscle relaxant (specifically, succinylcholine). The triggering substances release calcium stores from the sarcoplasmic reticulum and may promote entry of calcium from the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience: acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even arrest, and myoglobinuria with a risk for renal failure. In nearly all cases, the first manifestations of MH (tachycardia and tachypnea) occur in the operating room; however, MH may also occur in the early postoperative period. There is mounting evidence that some affected individuals will also develop MH with exercise and/or on exposure to hot environments. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high.
Mitochondrial DNA depletion syndrome 2
MedGen UID:
461100
Concept ID:
C3149750
Disease or Syndrome
TK2-related mitochondrial DNA (mtDNA) depletion syndrome is a phenotypic continuum that ranges from severe to mild. To date, approximately 45 individuals with a molecularly confirmed diagnosis have been reported. The most typical presentation, which occurs in infants and children, is progressive muscle disease characterized by generalized hypotonia, proximal muscle weakness, loss of previously acquired motor skills, poor feeding, and respiratory difficulties leading to respiratory failure and death within a few years after diagnosis. Other severe presentations include: Rapidly progressive proximal muscle weakness in newborns with encephalopathy, epilepsy, and early death; A spinal muscular atrophy-like presentation; Progressive myopathy with dystrophic changes (including sensorineural hearing loss); Hepatomegaly with elevated liver enzymes associated with the severe early-onset myopathy. Milder presentations include: Late-onset proximal muscle weakness and prolonged survival; Adult-onset forms with progressive mitochondrial myopathy; Chronic progressive external ophthalmoplegia with proximal muscle weakness associated with multiple mtDNA deletions and no mtDNA depletion.
Myopathy, lactic acidosis, and sideroblastic anemia 2
MedGen UID:
462152
Concept ID:
C3150802
Disease or Syndrome
Myopathy, lactic acidosis, and sideroblastic anemia-2 is an autosomal recessive disorder of the mitochondrial respiratory chain. The disorder shows marked phenotypic variability: some patients have a severe multisystem disorder from infancy, including cardiomyopathy and respiratory insufficiency resulting in early death, whereas others present in the second or third decade of life with sideroblastic anemia and mild muscle weakness (summary by Riley et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of MLASA, see MLASA1 (600462).
Mitochondrial DNA depletion syndrome 9 (encephalomyopathic with methylmalonic aciduria)
MedGen UID:
462826
Concept ID:
C3151476
Disease or Syndrome
Mitochondrial DNA depletion syndrome-9 is a severe autosomal recessive disorder characterized by infantile onset of hypotonia, lactic acidosis, severe psychomotor retardation, progressive neurologic deterioration, and excretion of methylmalonic acid. Some patients die in early infancy (summary by Rouzier et al., 2010). For a discussion of genetic heterogeneity of mtDNA depletion syndromes, see MTDPS1 (603041).
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 hepatocerebral mitochondrial DNA depletion syndrome (multisystem disease in neonates) and isolated hepatic disease later in infancy or childhood. The majority of affected individuals have the multisystem illness with hepatic disease (cholestasis) and neurologic dysfunction evident within weeks of birth. They subsequently manifest severe hypotonia, developmental regression, and typical rotary nystagmus that evolves into opsoclonus. 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.
Mitochondrial myopathy, infantile, due to reversible cytochrome c oxidase deficiency
MedGen UID:
463248
Concept ID:
C3151898
Disease or Syndrome
Infantile mitochondrial myopathy due to reversible COX deficiency is a rare mitochondrial disorder characterized by onset in infancy of severe hypotonia and generalized muscle weakness associated with lactic acidosis, but is distinguished from other mitochondrial disorders in that affected individuals recover spontaneously after 1 year of age (summary by Mimaki et al., 2010). See also transient infantile liver failure (LFIT; 613070), which is a similar disorder.
Mitochondrial encephalo-cardio-myopathy due to TMEM70 deficiency
MedGen UID:
481329
Concept ID:
C3279699
Disease or Syndrome
MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 3
MedGen UID:
481338
Concept ID:
C3279708
Disease or Syndrome
Combined oxidative phosphorylation deficiency 8
MedGen UID:
481423
Concept ID:
C3279793
Disease or Syndrome
COXPD8 is an autosomal recessive disorder due to dysfunction of the mitochondrial respiratory chain. The main clinical manifestation is a lethal infantile hypertrophic cardiomyopathy, but there may also be subtle skeletal muscle and brain involvement. Biochemical studies show combined respiratory chain complex deficiencies in complexes I, III, and IV in cardiac muscle, skeletal muscle, and brain. The liver is not affected (summary by Gotz et al., 2011). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Multiple mitochondrial dysfunctions syndrome 2
MedGen UID:
482008
Concept ID:
C3280378
Disease or Syndrome
Encephalopathy, lethal, due to defective mitochondrial and peroxisomal fission
MedGen UID:
482290
Concept ID:
C3280660
Disease or Syndrome
Encephalopathy due to defective mitochondrial and peroxisomal fission is a rare autosomal dominant systemic disorder resulting in lack of neurologic development and death in infancy (summary by Waterham et al., 2007).
Pyruvate dehydrogenase lipoic acid synthetase deficiency
MedGen UID:
482517
Concept ID:
C3280887
Disease or Syndrome
Pyruvate dehydrogenase lipoic acid synthetase deficiency is an autosomal recessive disorder of mitochondrial metabolism characterized by early-onset lactic acidosis, severe encephalomyopathy, and a pyruvate oxidation defect (Mayr et al., 2011).
Encephalomyopathy, mitochondrial, due to voltage-dependent anion channel deficiency
MedGen UID:
482736
Concept ID:
C3281106
Disease or Syndrome
Encephalopathy - hypertrophic cardiomyopathy - renal tubular disease
MedGen UID:
766288
Concept ID:
C3553374
Disease or Syndrome
Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency
MedGen UID:
766443
Concept ID:
C3553529
Disease or Syndrome
MEGDEL syndrome
MedGen UID:
766511
Concept ID:
C3553597
Disease or Syndrome
MITOCHONDRIAL PYRUVATE CARRIER DEFICIENCY
MedGen UID:
766521
Concept ID:
C3553607
Disease or Syndrome
Combined oxidative phosphorylation deficiency 11
MedGen UID:
766981
Concept ID:
C3554067
Disease or Syndrome
COXPD11 is a severe multisystemic autosomal recessive disorder characterized by neonatal hypotonia and lactic acidosis. Affected individuals may have respiratory insufficiency, foot deformities, or seizures, and all reported patients have died in infancy. Biochemical studies show deficiencies of multiple mitochondrial respiratory enzymes (summary by Garcia-Diaz et al., 2012). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Leukoencephalopathy - thalamus and brainstem anomalies - high lactate
MedGen UID:
766993
Concept ID:
C3554079
Disease or Syndrome
Combined oxidative phosphorylation defect type 14
MedGen UID:
767082
Concept ID:
C3554168
Disease or Syndrome
MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 3
MedGen UID:
815495
Concept ID:
C3809165
Disease or Syndrome
MITOCHONDRIAL DNA DEPLETION SYNDROME 12 (CARDIOMYOPATHIC TYPE)
MedGen UID:
815773
Concept ID:
C3809443
Disease or Syndrome
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 17
MedGen UID:
815856
Concept ID:
C3809526
Disease or Syndrome
MITOCHONDRIAL DNA DEPLETION SYNDROME 13 (ENCEPHALOMYOPATHIC TYPE)
MedGen UID:
815922
Concept ID:
C3809592
Disease or Syndrome
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 18
MedGen UID:
816331
Concept ID:
C3810001
Disease or Syndrome
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 19
MedGen UID:
816385
Concept ID:
C3810055
Disease or Syndrome
CARBONIC ANHYDRASE VA DEFICIENCY, HYPERAMMONEMIA DUE TO
MedGen UID:
816734
Concept ID:
C3810404
Disease or Syndrome
Glycogen storage disease, type VI
MedGen UID:
6643
Concept ID:
C0017925
Disease or Syndrome
Glycogen storage disease type VI (GSD VI), a disorder of glycogenolysis caused by deficiency of hepatic glycogen phosphorylase, is characterized in the untreated child by hepatomegaly, growth retardation, ketotic hypoglycemia after an overnight fast, and mild hypoglycemia after prolonged fasting (e.g., during an illness). It is usually a relatively mild disorder that presents in infancy and childhood; however, severe and recurrent hypoglycemia, severe hepatomegaly, and post-prandial lactic acidosis have been described. The risk of hepatic adenoma formation in late childhood and adulthood is theoretically increased. Clinical and biochemical abnormalities may resolve with age; most adults are asymptomatic. Hypoglycemia can occur during pregnancy.

Recent clinical studies

Etiology

Sawyer AJ, Haley HL, Baty SR, McGuffey GE, Eiland EH 3rd
Am J Kidney Dis 2014 Sep;64(3):457-9. Epub 2014 Jun 21 doi: 10.1053/j.ajkd.2014.04.032. [Epub ahead of print] PMID: 24961626
Ncomanzi D, Sicat RM, Sundararajan K
J Med Case Rep 2014 May 21;8:159. doi: 10.1186/1752-1947-8-159. [Epub ahead of print] PMID: 24884658Free PMC Article
Hussain MI, Hall BM, Depczynski B, Connor SJ
Diabetes Res Clin Pract 2014 Jul;105(1):e6-8. Epub 2014 Jan 8 doi: 10.1016/j.diabres.2013.12.055. [Epub ahead of print] PMID: 24877743
De Corte W, Vuylsteke S, De Waele JJ, Dhondt AW, Decruyenaere J, Vanholder R, Hoste EA
J Crit Care 2014 Aug;29(4):650-5. Epub 2014 Mar 5 doi: 10.1016/j.jcrc.2014.02.019. [Epub ahead of print] PMID: 24636927
Vecchio S, Giampreti A, Petrolini VM, Lonati D, Protti A, Papa P, Rognoni C, Valli A, Rocchi L, Rolandi L, Manzo L, Locatelli CA
Clin Toxicol (Phila) 2014 Feb;52(2):129-35. Epub 2013 Nov 28 doi: 10.3109/15563650.2013.860985. [Epub ahead of print] PMID: 24283301

Diagnosis

Kraut JA, Madias NE
N Engl J Med 2014 Dec 11;371(24):2309-19. doi: 10.1056/NEJMra1309483. PMID: 25494270
Ncomanzi D, Sicat RM, Sundararajan K
J Med Case Rep 2014 May 21;8:159. doi: 10.1186/1752-1947-8-159. [Epub ahead of print] PMID: 24884658Free PMC Article
Lau E, Mazer J, Carino G
BMJ Case Rep 2013 Oct 14;2013 doi: 10.1136/bcr-2013-201015. PMID: 24127377
Invernizzi F, Tigano M, Dallabona C, Donnini C, Ferrero I, Cremonte M, Ghezzi D, Lamperti C, Zeviani M
Hum Mutat 2013 Dec;34(12):1619-22. Epub 2013 Sep 23 doi: 10.1002/humu.22441. [Epub ahead of print] PMID: 24014394Free PMC Article
Sia P, Plumb TJ, Fillaus JA
Am J Kidney Dis 2013 Sep;62(3):633-7. Epub 2013 Jun 4 doi: 10.1053/j.ajkd.2013.03.036. [Epub ahead of print] PMID: 23759296

Therapy

Sawyer AJ, Haley HL, Baty SR, McGuffey GE, Eiland EH 3rd
Am J Kidney Dis 2014 Sep;64(3):457-9. Epub 2014 Jun 21 doi: 10.1053/j.ajkd.2014.04.032. [Epub ahead of print] PMID: 24961626
Ncomanzi D, Sicat RM, Sundararajan K
J Med Case Rep 2014 May 21;8:159. doi: 10.1186/1752-1947-8-159. [Epub ahead of print] PMID: 24884658Free PMC Article
Hussain MI, Hall BM, Depczynski B, Connor SJ
Diabetes Res Clin Pract 2014 Jul;105(1):e6-8. Epub 2014 Jan 8 doi: 10.1016/j.diabres.2013.12.055. [Epub ahead of print] PMID: 24877743
De Corte W, Vuylsteke S, De Waele JJ, Dhondt AW, Decruyenaere J, Vanholder R, Hoste EA
J Crit Care 2014 Aug;29(4):650-5. Epub 2014 Mar 5 doi: 10.1016/j.jcrc.2014.02.019. [Epub ahead of print] PMID: 24636927
Lau E, Mazer J, Carino G
BMJ Case Rep 2013 Oct 14;2013 doi: 10.1136/bcr-2013-201015. PMID: 24127377

Prognosis

Kraut JA, Madias NE
N Engl J Med 2014 Dec 11;371(24):2309-19. doi: 10.1056/NEJMra1309483. PMID: 25494270
Hussain MI, Hall BM, Depczynski B, Connor SJ
Diabetes Res Clin Pract 2014 Jul;105(1):e6-8. Epub 2014 Jan 8 doi: 10.1016/j.diabres.2013.12.055. [Epub ahead of print] PMID: 24877743
De Corte W, Vuylsteke S, De Waele JJ, Dhondt AW, Decruyenaere J, Vanholder R, Hoste EA
J Crit Care 2014 Aug;29(4):650-5. Epub 2014 Mar 5 doi: 10.1016/j.jcrc.2014.02.019. [Epub ahead of print] PMID: 24636927
Sia P, Plumb TJ, Fillaus JA
Am J Kidney Dis 2013 Sep;62(3):633-7. Epub 2013 Jun 4 doi: 10.1053/j.ajkd.2013.03.036. [Epub ahead of print] PMID: 23759296
Kim HJ, Son YK, An WS
PLoS One 2013;8(6):e65283. Epub 2013 Jun 5 doi: 10.1371/journal.pone.0065283. PMID: 23755210Free PMC Article

Clinical prediction guides

De Corte W, Vuylsteke S, De Waele JJ, Dhondt AW, Decruyenaere J, Vanholder R, Hoste EA
J Crit Care 2014 Aug;29(4):650-5. Epub 2014 Mar 5 doi: 10.1016/j.jcrc.2014.02.019. [Epub ahead of print] PMID: 24636927
Vecchio S, Giampreti A, Petrolini VM, Lonati D, Protti A, Papa P, Rognoni C, Valli A, Rocchi L, Rolandi L, Manzo L, Locatelli CA
Clin Toxicol (Phila) 2014 Feb;52(2):129-35. Epub 2013 Nov 28 doi: 10.3109/15563650.2013.860985. [Epub ahead of print] PMID: 24283301
Invernizzi F, Tigano M, Dallabona C, Donnini C, Ferrero I, Cremonte M, Ghezzi D, Lamperti C, Zeviani M
Hum Mutat 2013 Dec;34(12):1619-22. Epub 2013 Sep 23 doi: 10.1002/humu.22441. [Epub ahead of print] PMID: 24014394Free PMC Article
Baruffini E, Dallabona C, Invernizzi F, Yarham JW, Melchionda L, Blakely EL, Lamantea E, Donnini C, Santra S, Vijayaraghavan S, Roper HP, Burlina A, Kopajtich R, Walther A, Strom TM, Haack TB, Prokisch H, Taylor RW, Ferrero I, Zeviani M, Ghezzi D
Hum Mutat 2013 Nov;34(11):1501-9. Epub 2013 Sep 17 doi: 10.1002/humu.22393. [Epub ahead of print] PMID: 23929671Free PMC Article
Kim HJ, Son YK, An WS
PLoS One 2013;8(6):e65283. Epub 2013 Jun 5 doi: 10.1371/journal.pone.0065283. PMID: 23755210Free PMC Article

Recent systematic reviews

Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK
JAMA 2014 Dec 24-31;312(24):2668-75. doi: 10.1001/jama.2014.15298. PMID: 25536258
Renda F, Mura P, Finco G, Ferrazin F, Pani L, Landoni G
Eur Rev Med Pharmacol Sci 2013 Feb;17 Suppl 1:45-9. PMID: 23436666
Cayley WE Jr
Am Fam Physician 2010 Nov 1;82(9):1068-70. PMID: 21121550
Salpeter SR, Greyber E, Pasternak GA, Salpeter EE
Cochrane Database Syst Rev 2010 Apr 14;(4):CD002967. doi: 10.1002/14651858.CD002967.pub4. PMID: 20393934
Salpeter SR, Greyber E, Pasternak GA, Salpeter Posthumous EE
Cochrane Database Syst Rev 2010 Jan 20;(1):CD002967. doi: 10.1002/14651858.CD002967.pub3. PMID: 20091535

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