3-Methylglutaconic Aciduria, Type Iv (MGCA4)

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Disease Ontology 12 DOID:0110006 OMIM® 57 250951 ICD10 via Orphanet 33 E71.1 UMLS via Orphanet 71 C0574085 C1855126

Orphanet 58 ORPHA67048 MedGen 41 C1855126 SNOMED-CT via HPO 68 103276001 128306009 128613002 15188001 190882007 193570009 204368006 204878001 205294008 221360009 224958001 228156007 237630007 237950009 246545002 247032003 247053007 247578003 248409006 258211005 271327008 271611007 302215000 302866003 313307000 343087000 349006 36440009 37280007 396232000 397790002 398151007 398152000 415116008 432788009 57809008 70397008 75183008 77981007 84757009 85898001 91138005 91175000 91273001 95828007 more UMLS 70 C0574085 C1855126

GARD : ²⁰ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 67048 Definition 3-methylglutaconic aciduria (3-MGA) type IV, or unclassified 3-MGA, is a clinically heterogeneous disorder characterised by increased 3-methylglutaconic acid excretion in individuals that cannot be classified as having one of the other forms of 3-MGA (3-MGA I, II or III). Epidemiology The prevalence of this disorder is unknown. Clinical description Patients usually present during the first year of life with neurological findings including psychomotor retardation, hypotonia, developmental delay, seizures and progressive spasticity, together with severe failure to thrive. Cardiomyopathy, hepatic dysfunction, eye anomalies, microcephaly, deafness, dysmorphism, neonatal hypoglycaemia, thrombocytopaenia and lactic acidosis have also been reported. Cerebellar dysgenesis may be revealed by magnetic resonance imaging. In contrast, a small number of asymptomatic patients have been diagnosed as having 3-MGA type IV. Etiology The aetiology remains unknown: unlike patients with 3-MGA type I, individuals with 3MGA type IV display normal 3-methylglutaconyl-CoA hydratase activity in cultured fibroblasts. Mitochondrial respiratory chain abnormalities have been detected in some 3MGA type IV patients but the clinical heterogeneity associated with this disorder suggests that the 3-methylglutaconic aciduria seen in 3-MGA type IV patients may result from a variety of causes and genetic factors. Diagnostic methods 3-methylglutaconic aciduria can be diagnosed by analysis of urinary organic acid excretion but specific diagnosis of 3-MGA type IV requires exclusion of all other forms of 3-MGA. As the genetic factors responsible for the other forms of 3-MGA have now been determined, molecular analysis provides a valuable tool for accurate diagnosis. Differential diagnosis 3-MGA type IV can be distinguished from the type I disorder by normal excretion of 3-hydroxyisovaleric acid. 3-MGA type II may be excluded by the mode of inheritance (transmission is X-linked recessive in 3-MGA type II) and on the basis of the clinical phenotype (the type II disorder is characterised by neutropaenia, skeletal myopathy, dilated cardiomyopathy and growth delay). Depending on the manifestations present, clinical differentiation of types III and IV may be more problematic, but the occurrence of 3-MGA type III is largely restricted to the Iraqi-Jewish population. In addition to other forms of 3-MGA, the differential diagnosis should also include cerebral palsy, dilated cardiomyopathy with ataxia (see this term) and other organic acidurias. Genetic counseling The disorder has been reported to be inherited as an autosomal recessive trait. Management and treatment At present there is no effective treatment for 3-MGA type IV and a leucine-restricted diet appears to be of no benefit. Prognosis The prognosis depends on the clinical phenotype but the neurological complications can be severe with a potentially fatal disease course.

MalaCards based summary : 3-Methylglutaconic Aciduria, Type Iv, also known as 3-methylglutaconic aciduria type 4, is related to 3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome and 3-methylglutaconic aciduria. An important gene associated with 3-Methylglutaconic Aciduria, Type Iv is SERAC1 (Serine Active Site Containing 1), and among its related pathways/superpathways are Lysosome and TBC/RABGAPs. Affiliated tissues include eye and liver, and related phenotypes are intellectual disability and spasticity

Disease Ontology : ¹² A 3-methylglutaconic aciduria that is characterized by mild or intermittent urinary excretion of 3-methylglutaconic acid.

OMIM® : ⁵⁷ The category of 3-methylglutaconic aciduria type IV (MGCA4) represents a heterogeneous unclassified group of patients who share mild or intermittent urinary excretion of 3-methylglutaconic acid. MGCA excretion is a nonspecific finding observed in many other disorders caused by defects in mitochondrial energy metabolism (Gunay-Aygun, 2005). For a general phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA1 (250950) (250951) (Updated 20-May-2021)

Clinical features from OMIM®:

250951 (Updated 20-May-2021)

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