3-Methylglutaconic Aciduria, Type I (MGCA1)

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Disease Ontology 12 DOID:0110002 OMIM 56 250950 OMIM Phenotypic Series 56 PS250950 MeSH 43 D000592 ICD10 via Orphanet 33 E71.1

UMLS via Orphanet 72 C0342727 C0342728 Orphanet 58 ORPHA67046 MedGen 41 C0342727 SNOMED-CT via HPO 68 128613002 162294008 165232002 192965001 224958001 22811006 229721007 230233000 237630007 237950009 246545002 247762003 258211005 271327008 271611007 278849000 29164008 298282001 302866003 313307000 36440009 371632003 386806002 41497008 418143002 432788009 44913001 52522001 58593005 59455009 62415009 70835005 76976005 8011004 80515008 84757009 85102008 86854008 91175000 more UMLS 71 C0342727 C0342728 C1306856

NIH Rare Diseases : ⁵² The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 67046 Definition 3-methylglutaconic aciduria (3-MGA) type I is an inborn error of leucine metabolism with a variable clinical phenotype ranging from mildly delayed speech to psychomotor retardation, coma, failure to thrive, metabolic acidosis and dystonia . Epidemiology The disorder is very rare with less than 20 cases reported in the literature. Clinical description Clinical manifestations usually become apparent in the neonatal period or during infancy but the diagnosis may not be made until childhood. Some of the reported patients also displayed hypoglycaemia, spastic quadriparesis, microcephaly , progressive neurological deficit, seizures , vomiting, atrophy of the basal ganglia, severe hypotonia and hepatomegly. Etiology The syndrome is caused by mutations in the AUH gene (chromosome 9) encoding 3-methylglutaconyl-CoA hydratase, an enzyme involved in leucine degradation. Diagnostic methods As the clinical picture is variable and nonspecific, diagnosis can be made by assay of 3-methylglutaconyl-CoA hydratase activity in fibroblasts or leukocytes , quantitative analysis of urinary organic acid excretion or, more recently, analysis of bodily fluids by NMR spectroscopy. Differential diagnosis Patients with 3-MGA type I can be distinguished from those with other forms of 3-MGA (types II, III and IV; see these terms) by the distinctive pattern of metabolite excretion: 3-methylglutaconic acid levels are highly elevated (higher than those detected in other forms of 3-MGA) whereas methylglutaric acid levels are usually only slightly elevated, and there is a high level of 3-hydroxyisovaleric acid excretion (not present in other forms of 3-MGA). Antenatal diagnosis Prenatal diagnosis should be possible through detection of high levels of 3-hydroxyisovaleric acid in the amniotic fluid or through enzyme analysis of cultured amniocytes . Genetic counseling The syndrome is inherited as an autosomal recessive trait . Management and treatment Treatment is largely symptomatic but dietary management with a modest leucine restriction and supplementation with L-carnitine may be beneficial in some cases. Visit the Orphanet disease page for more resources.

MalaCards based summary : 3-Methylglutaconic Aciduria, Type I, also known as 3-methylglutaconyl-coa hydratase deficiency, is related to imerslund-grasbeck syndrome 1 and megaloblastic anemia, and has symptoms including athetosis and cerebellar ataxia. An important gene associated with 3-Methylglutaconic Aciduria, Type I is AUH (AU RNA Binding Methylglutaconyl-CoA Hydratase), and among its related pathways/superpathways are Diseases of metabolism and Vitamin digestion and absorption. Affiliated tissues include brain, eye and skeletal muscle, and related phenotypes are failure to thrive and 3-methylglutaconic aciduria

Disease Ontology : ¹² A 3-methylglutaconic aciduria that has material basis in homozygous or compound heterozygous mutation in the AUH gene on chromosome 9q22.

Genetics Home Reference : ²⁵ 3-methylglutaconyl-CoA hydratase deficiency is an inherited condition that causes neurological problems. Beginning in infancy to early childhood, children with this condition often have delayed development of mental and motor skills (psychomotor delay), speech delay, involuntary muscle cramping (dystonia), and spasms and weakness of the arms and legs (spastic quadriparesis). Affected individuals can also have optic atrophy, which is the degeneration (atrophy) of nerve cells that carry visual information from the eyes to the brain. In some cases, signs and symptoms of 3-methylglutaconyl-CoA hydratase deficiency begin in adulthood, often in a person's twenties or thirties. These individuals have damage to a type of brain tissue called white matter (leukoencephalopathy), which likely contributes to progressive problems with speech (dysarthria), difficulty coordinating movements (ataxia), stiffness (spasticity), optic atrophy, and a decline in intellectual function (dementia). Affected individuals who show symptoms of 3-methylglutaconyl-CoA hydratase deficiency in childhood often go on to develop leukoencephalopathy and other neurological problems in adulthood. All people with 3-methylglutaconyl-CoA hydratase deficiency accumulate large amounts of a substance called 3-methylglutaconic acid in their body fluids. As a result, they have elevated levels of acid in their blood (metabolic acidosis) and excrete large amounts of acid in their urine (aciduria). 3-methylglutaconyl-CoA hydratase deficiency is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels 3-methylglutaconic acid in urine (3-methylglutaconic aciduria). People with 3-methylglutaconyl-CoA hydratase deficiency also have high urine levels of another acid called 3-methylglutaric acid.

OMIM : ⁵⁶ 3-Methylglutaconic aciduria type I (MGCA1) is a rare autosomal recessive disorder of leucine catabolism. The metabolic landmark is urinary excretion of 3-methylglutaconic acid (3-MGA) and its derivatives 3-methylglutaric acid (3-MG) and 3-hydroxyisovaleric acid (3-HIVA). Two main presentations have been described: one with onset in childhood associated with the nonspecific finding of psychomotor retardation, and the other with onset in adulthood of a progressive neurodegenerative disorder characterized by ataxia, spasticity, and sometimes dementia; these patients develop white matter lesions in the brain. However, some asymptomatic pediatric patients have been identified by newborn screening and show no developmental abnormalities when reexamined later in childhood (summary by Wortmann et al., 2010). (250950)

UniProtKB/Swiss-Prot : ⁷³ 3-methylglutaconic aciduria 1: An inborn error of leucine metabolism. It leads to an autosomal recessive syndrome with variable clinical phenotype, ranging from delayed speech development to severe psychomotor retardation, coma, failure to thrive, metabolic acidosis and dystonia. MGCA1 can be distinguished from other forms of MGCA by the pattern of metabolite excretion: 3-methylglutaconic acid levels are higher than those detected in other forms, whereas methylglutaric acid levels are usually only slightly elevated and there is a high level of 3- hydroxyisovaleric acid excretion (not present in other MGCA forms).

Wikipedia : ⁷⁴ 3-Methylglutaconic aciduria (MGA) is any of at least five metabolic disorders that impair the body's... more...

Clinical features from OMIM:

250950

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