Preferred Label : 3-methylglutaconic aciduria, type I;
Symbol : MGCA1;
CISMeF acronym : MGA1; MGCA1;
Type : Phenotype, molecular basis known;
Alternative titles and symbols : 3-methylglutaconyl-coa hydratase deficiency; 3-mg-coa-hydratase deficiency; MGA1; Mga, type I;
Description : Type I MGCA is a rare autosomal recessive disorder of leucine catabolism. The metabolic
landmark is urinary excretion of 3-methylglutaconic acid (3-MGA) and its derivatives
3-methylglutaric acid (3-MG) and 3-hydroxyisovaleric acid (3-HIVA). Two main presentations
have been described: 1 with onset in childhood associated with the nonspecific finding
of psychomotor retardation, and the other with onset in adulthood of a progressive
neurodegenerative disorder characterized by ataxia, spasticity, and sometimes dementia;
these patients develop white matter lesions in the brain. However, some asymptomatic
pediatric patients have been identified by newborn screening and show no developmental
abnormalities when reexamined later in childhood (summary by Wortmann et al., 2010).
- Genetic Heterogeneity and Classification of Methylglutaconic Aciduria Methylglutaconic
aciduria is a clinically and genetically heterogeneous disorder. Type II MGCA, also
known as Barth syndrome (BTHS; 302060), is caused by mutation in the tafazzin gene
(TAZ; 300394) on chromosome Xq28. It is characterized by mitochondrial cardiomyopathy,
short stature, skeletal myopathy, and recurrent infections; cognitive development
is normal. Type III MGCA (258501), caused by mutation in the OPA3 gene (606580) on
chromosome 19q13.2-q13.3, occurs in Iraqi Jews and involves optic atrophy, movement
disorder, and spastic paraplegia. In types II and III, the elevations of 3-methylglutaconate
and 3-methylglutarate in urine are modest. Type IV MGCA (250951) represents an unclassified
group of patients who have severe psychomotor retardation and cerebellar dysgenesis.
Type V MGCA (610198), caused by mutation in the DNAJC19 gene (608977) on chromosome
3q26.33, is characterized by early-onset dilated cardiomyopathy with conduction defects,
nonprogressive cerebellar ataxia, testicular dysgenesis, and growth failure in addition
to 3-methylglutaconic aciduria (Chitayat et al., 1992; Davey et al., 2006). Eriguchi
et al. (2006) noted that type I MGCA is very rare, with only 13 patients reported
in the literature as of 2003.;
Inheritance : Autosomal recessive;
Molecular basis : Caused by mutation in the AU-specific RNA-binding protein gene (AUH, 600529.0001);
Laboratory abnormalities : Increased urinary 3-methylglutaconic acid; Increased urinary hydroxyisovaleric acid; Decreased activity of 3-methylglutaconyl-CoA hydratase;
Prefixed ID : #250950;
Origin ID : 250950;
UMLS CUI : C0342727;
Automatic exact mappings (from CISMeF team)
- Currated CISMeF NLP mapping
- DO Cross reference
- Genes related to phenotype
- HPO term(s)
- ORDO concept(s)
- See also inter- (CISMeF)
- Semantic type(s)
- UMLS correspondences (same concept)
- Validated automatic mappings to NTBT
