3-Methylglutaconic Aciduria, Type V (MGCA5)

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Disease Ontology 12 DOID:0110000 OMIM 56 610198 OMIM Phenotypic Series 56 PS250950 MeSH 43 D002311 ICD10 via Orphanet 33 E71.1

UMLS via Orphanet 72 C1857776 Orphanet 58 ORPHA66634 MedGen 41 C1857776 SNOMED-CT via HPO 68 111975006 128613002 166603001 166643006 194424005 195021004 199612005 204878001 204888000 204890004 205294008 22033007 228156007 237950009 246545002 247578003 248200007 258211005 26544005 268228006 276411001 28987007 30721006 313307000 32003007 33595009 34168003 34911001 394679006 398206004 398302004 399020009 40930008 42343007 430099007 44666001 4984008 52767006 609225004 75183008 76976005 84114007 84757009 85102008 91138005 91175000 94706008 95281009 9748009 more UMLS 71 C1857776 C4039473

Genetics Home Reference : ²⁵ Dilated cardiomyopathy with ataxia (DCMA) syndrome is an inherited condition characterized by heart problems, movement difficulties, and other features affecting multiple body systems. Beginning in infancy to early childhood, most people with DCMA syndrome develop dilated cardiomyopathy, which is a condition that weakens and enlarges the heart, preventing it from pumping blood efficiently. Some affected individuals also have long QT syndrome, which is a heart condition that causes the cardiac muscle to take longer than usual to recharge between beats. The irregular heartbeats (arrhythmia) can lead to fainting (syncope) or cardiac arrest and sudden death. Rarely, heart problems improve over time; however, in most cases of DCMA syndrome, affected individuals do not survive past childhood due to heart failure. A small percentage of people with DCMA syndrome have no heart problems at all. By age 2, children with DCMA syndrome have problems with coordination and balance (ataxia). These movement problems can result in delay of motor skills such as standing and walking, but most older children with DCMA syndrome can walk without support. In addition to heart problems and movement difficulties, most individuals with DCMA syndrome grow slowly before and after birth, which leads to short stature. Additionally, many affected individuals have mild intellectual disability. Many males with DCMA syndrome have genital abnormalities such as undescended testes (cryptorchidism) or the urethra opening on the underside of the penis (hypospadias). Other common features of DCMA syndrome include unusually small red blood cells (microcytic anemia), which can cause pale skin; an abnormal buildup of fats in the liver (hepatic steatosis), which can damage the liver; and the degeneration of nerve cells that carry visual information from the eyes to the brain (optic nerve atrophy), which can lead to vision loss. DCMA syndrome is associated with increased levels of a substance called 3-methylglutaconic acid in the urine. The amount of acid does not appear to influence the signs and symptoms of the condition. DCMA syndrome is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels of 3-methylglutaconic acid in urine (3-methylglutaconic aciduria). People with DCMA syndrome also have high urine levels of another acid called 3-methylglutaric acid.

MalaCards based summary : 3-Methylglutaconic Aciduria, Type V, also known as mga5, is related to 3-methylglutaconic aciduria, type iv and 3-methylglutaconic aciduria, type i, and has symptoms including muscle weakness and cerebellar ataxia. An important gene associated with 3-Methylglutaconic Aciduria, Type V is DNAJC19 (DnaJ Heat Shock Protein Family (Hsp40) Member C19), and among its related pathways/superpathways are Metabolism of proteins and Mitochondrial protein import. Affiliated tissues include heart, testes and eye, and related phenotypes are ataxia and dilated cardiomyopathy

Disease Ontology : ¹² A 3-methylglutaconic aciduria that has material basis in homozygous mutation in the DNAJC19 gene on chromosome 3q26.

NIH Rare Diseases : ⁵² The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 66634 Definition Dilated cardiomyopathy with ataxia (DCMA) is characterized by severe early onset (before the age of three years) dilated cardiomyopathy (DCM) with conduction defects (long QT syndrome ), non-progressive cerebellar ataxia, testicular dysgenesis, and 3-methylglutaconic aciduria. Epidemiology To date, all cases of DCMA reported involve individuals from the Dariusleut Hutterite population, an endogamous population of the Great Plains region of Canada and the northern United States. Clinical description Prenatal or postnatal growth failure, significant motor delay (due to cerebellar syndrome with ataxia) and male genital anomalies (ranging from isolated cryptorchidism to severe perineal hypospadias) are very frequent clinical signs. Additional features include optic atrophy, a mild increase in hepatic enzymes with microvesicular hepatic steatosis, a normochromic microcytic anemia , and mild to borderline non-progressive intellectual deficit. Etiology DCMA is caused by mutation of the DNAJC19 gene (encoding the DNAJC19 protein localized to the mitochondria in cardiac myocytes). Differential diagnosis DCMA syndrome shares some clinical features with the X-linked Barth syndrome and the other 3-methylglutaconic acidurias (types I, III and IV; see these terms). Genetic counseling DCMA is an autosomal recessive condition. Prognosis In a clinical study of 18 DCMA patients, over 70% of patients died from either progressive cardiac failure or sudden cardiac death. Improvement with standard medical treatment or complete resolution of the DCM has been reported in some patients. Visit the Orphanet disease page for more resources.

OMIM : ⁵⁶ 3-Methylglutaconic aciduria type V is an autosomal recessive disorder characterized by the onset of dilated or noncompaction cardiomyopathy in infancy or early childhood. Many patients die of cardiac failure. Other features include microcytic anemia, growth retardation, mild ataxia, mild muscle weakness, genital anomalies in males, and increased urinary excretion of 3-methylglutaconic acid. Some patients may have optic atrophy or delayed psychomotor development (summary by Davey et al., 2006 and Ojala et al., 2012). For a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950). (610198)

UniProtKB/Swiss-Prot : ⁷³ 3-methylglutaconic aciduria 5: An autosomal recessive disorder characterized by early-onset dilated cardiomyopathy, growth failure, cerebellar ataxia causing significant motor delays, testicular dysgenesis, growth failure and significant increases in urine organic acids, particularly 3-methylglutaconic acid and 3-methylglutaric acid.

Clinical features from OMIM:

610198

Search Clinical Trials , NIH Clinical Center for 3-Methylglutaconic Aciduria, Type V

Search GEO for disease gene expression data for 3-Methylglutaconic Aciduria, Type V.