3-Methylglutaconic Aciduria, Type I

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OMIM 57 250950 Disease Ontology 12 DOID:0110002 Orphanet 59 ORPHA67046 UMLS via Orphanet 74 C0342727 C0342728 ICD10 via Orphanet 34 E71.1

MedGen 42 C0342727 MeSH 44 D000592 SNOMED-CT via HPO 69 258211005 165232002 271611007 76976005 247762003 162294008 229721007 29164008 62415009 128613002 246545002 313307000 84757009 91175000 85102008 371632003 8011004 224958001 298282001 86854008 36440009 432788009 59455009 237630007 271327008 302866003 278849000 418143002 52522001 230233000 70835005 80515008 44913001 58593005 22811006 41497008 192965001 237950009 386806002 more UMLS 73 C0342727 C1306856 C0342728

NIH Rare Diseases : ⁵³ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 67046Disease definition3-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.EpidemiologyThe disorder is very rare with less than 20 cases reported in the literature.Clinical descriptionClinical 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.EtiologyThe syndrome is caused by mutations in the AUH gene (chromosome 9) encoding 3-methylglutaconyl-CoA hydratase, an enzyme involved in leucine degradation.Diagnostic methodsAs 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 diagnosisPatients 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 diagnosisPrenatal 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 counselingThe syndrome is inherited as an autosomal recessivetrait.Management and treatmentTreatment 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 megaloblastic anemia 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 Valine, leucine and isoleucine degradation and Diseases of metabolism. Affiliated tissues include brain, eye and skin, and related phenotypes are seizures and failure to thrive

OMIM : ⁵⁷ Type I MGCA is a rare autosomal recessive disorder of leucine catabolism. The metabolic landmark is urinary excretion of 3-methylglutaconic acid (3-MGA) and its derivatives 3-methylglutaric acid (3-MG) and 3-hydroxyisovaleric acid (3-HIVA). Two main presentations have been described: 1 with onset in childhood associated with the nonspecific finding of psychomotor retardation, and the other with onset in adulthood of a progressive neurodegenerative disorder characterized by ataxia, spasticity, and sometimes dementia; these patients develop white matter lesions in the brain. However, some asymptomatic pediatric patients have been identified by newborn screening and show no developmental abnormalities when reexamined later in childhood (summary by Wortmann et al., 2010). (250950)

UniProtKB/Swiss-Prot : ⁷⁵ 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. MGA1 can be distinguished from other forms of MGA 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 MGA forms).

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.

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

Wikipedia : ⁷⁶ 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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