MCID: 3MT015
MIFTS: 41

3-Methylglutaconic Aciduria, Type I

Categories: Genetic diseases, Rare diseases, Metabolic diseases, Cardiovascular diseases, Eye diseases

Aliases & Classifications for 3-Methylglutaconic Aciduria, Type I

MalaCards integrated aliases for 3-Methylglutaconic Aciduria, Type I:

Name: 3-Methylglutaconic Aciduria, Type I 54 25 13
3-Methylglutaconyl-Coa Hydratase Deficiency 12 50 24 25 56 71
3-Methylglutaconic Aciduria Type 1 12 24 56 14 69
Mga1 12 25 56 71
3mg-Coa Hydratase Deficiency 12 56 71
Mga Type I 12 50 71
Mgca1 25 71
Megaloblastic Anemia Due to Inborn Errors of Metabolism 69
3-Alpha-Methylglutaconyl-Coa Hydratase Deficiency 71
3 Methylglutaconyl Coa Hydratase Deficiency 50
3 Alpha Methylglutaconic Aciduria Type I 50
3-Alpha-Methylglutaconic Aciduria Type 1 71
3-@methylglutaconic Aciduria, Type I 69
Primary 3-Methylglutaconic Aciduria 25
3-Methylglutaconic Aciduria Type I 12
3 Methylglutaconic Aciduria Type 1 50
3-Mg-Coa-Hydratase Deficiency 25
3-Methylglutaconic Aciduria 1 71
3mg Coa Hydratase Deficiency 50
3-Mgca Type I 50
Mga, Type I 25
Auh Defect 25

Characteristics:

Orphanet epidemiological data:

56
3-methylglutaconic aciduria type 1
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
highly variable phenotype
adult onset of symptoms has been reported
some patients have no clinical symptoms and are detected by routine newborn screening


HPO:

32
3-methylglutaconic aciduria, type i:
Onset and clinical course phenotypic variability infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 56  
Inborn errors of metabolism


Summaries for 3-Methylglutaconic Aciduria, Type I

NIH Rare Diseases : 50 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. last updated: 3/5/2007

MalaCards based summary : 3-Methylglutaconic Aciduria, Type I, also known as 3-methylglutaconyl-coa hydratase deficiency, is related to megaloblastic anemia and 3-methylglutaconic aciduria, type v, and has symptoms including failure to thrive, dystonia and hepatomegaly. 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 Amino Acid metabolism. Affiliated tissues include brain, eye and skin.

UniProtKB/Swiss-Prot : 71 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.

OMIM : 54
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)

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

Related Diseases for 3-Methylglutaconic Aciduria, Type I

Graphical network of the top 20 diseases related to 3-Methylglutaconic Aciduria, Type I:



Diseases related to 3-Methylglutaconic Aciduria, Type I

Symptoms & Phenotypes for 3-Methylglutaconic Aciduria, Type I

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive

Head And Neck- Eyes:
optic atrophy

Genitourinary- Bladder:
urinary incontinence (adult)

Neurologic- Central Nervous System:
delayed motor development
dystonia
dysarthria
hyperreflexia
cognitive impairment
more
Metabolic Features:
metabolic acidosis

Laboratory- Abnormalities:
increased urinary 3-methylglutaconic acid
increased urinary hydroxyisovaleric acid
decreased activity of 3-methylglutaconyl-coa hydratase


Clinical features from OMIM:

250950

Human phenotypes related to 3-Methylglutaconic Aciduria, Type I:

56 32 (show all 27)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 56 32 hallmark (90%) Very frequent (99-80%) HP:0001508
2 dystonia 56 32 occasional (7.5%) Occasional (29-5%) HP:0001332
3 hepatomegaly 56 32 occasional (7.5%) Occasional (29-5%) HP:0002240
4 seizures 56 32 occasional (7.5%) Occasional (29-5%) HP:0001250
5 microcephaly 56 32 occasional (7.5%) Occasional (29-5%) HP:0000252
6 global developmental delay 56 32 occasional (7.5%) Frequent (79-30%) HP:0001263
7 coma 56 32 occasional (7.5%) Occasional (29-5%) HP:0001259
8 hypoglycemia 56 32 occasional (7.5%) Occasional (29-5%) HP:0001943
9 3-methylglutaconic aciduria 56 32 hallmark (90%) Very frequent (99-80%) HP:0003535
10 spastic tetraparesis 56 32 occasional (7.5%) Occasional (29-5%) HP:0001285
11 progressive cerebellar ataxia 56 32 occasional (7.5%) Occasional (29-5%) HP:0002073
12 delayed speech and language development 56 32 frequent (33%) Frequent (79-30%) HP:0000750
13 abnormality of the basal ganglia 56 32 occasional (7.5%) Occasional (29-5%) HP:0002134
14 optic atrophy 32 HP:0000648
15 dysarthria 32 HP:0001260
16 ataxia 32 HP:0001251
17 hyperreflexia 32 HP:0001347
18 cognitive impairment 32 HP:0100543
19 cerebral atrophy 32 HP:0002059
20 metabolic acidosis 32 HP:0001942
21 motor delay 32 HP:0001270
22 urinary incontinence 32 HP:0000020
23 leukoencephalopathy 32 HP:0002352
24 spastic tetraplegia 32 HP:0002510
25 febrile seizures 32 HP:0002373
26 short attention span 32 HP:0000736
27 athetosis 32 HP:0002305

UMLS symptoms related to 3-Methylglutaconic Aciduria, Type I:


athetosis, cerebellar ataxia

Drugs & Therapeutics for 3-Methylglutaconic Aciduria, Type I

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

Genetic Tests for 3-Methylglutaconic Aciduria, Type I

Genetic tests related to 3-Methylglutaconic Aciduria, Type I:

id Genetic test Affiliating Genes
1 3-Methylglutaconic Aciduria Type 1 24 AUH

Anatomical Context for 3-Methylglutaconic Aciduria, Type I

MalaCards organs/tissues related to 3-Methylglutaconic Aciduria, Type I:

39
Brain, Eye, Skin

Publications for 3-Methylglutaconic Aciduria, Type I

Articles related to 3-Methylglutaconic Aciduria, Type I:

id Title Authors Year
1
Phenotypic heterogeneity in two siblings with 3-methylglutaconic aciduria type I caused by a novel intragenic deletion. ( 21840233 )
2011
2
3-Methylglutaconic aciduria type I redefined: a syndrome with late-onset leukoencephalopathy. ( 20855850 )
2010
3
3-Methylglutaconic aciduria type I causes leukoencephalopathy of adult onset. ( 17130438 )
2006
4
NMR spectroscopic studies on the late onset form of 3-methylglutaconic aciduria type I and other defects in leucine metabolism. ( 16541463 )
2006
5
A molecular lesion in a Japanese patient with severe phenotype of 3-methylglutaconic aciduria type I. ( 16354225 )
2005
6
Direct nonisotopic assay of 3-methylglutaconyl-CoA hydratase in cultured human skin fibroblasts to specifically identify patients with 3-methylglutaconic aciduria type I. ( 15192029 )
2004
7
3-methylglutaconic aciduria type I in a boy with fever-associated seizures. ( 15033206 )
2004
8
Mutations in the AUH gene cause 3-methylglutaconic aciduria type I. ( 12655555 )
2003
9
3-methylglutaconic aciduria type I is caused by mutations in AUH. ( 12434311 )
2002
10
3-Methylglutaconic aciduria type I: clinical heterogeneity as a neurometabolic disease. ( 10070612 )
1999

Variations for 3-Methylglutaconic Aciduria, Type I

UniProtKB/Swiss-Prot genetic disease variations for 3-Methylglutaconic Aciduria, Type I:

71
id Symbol AA change Variation ID SNP ID
1 AUH p.Ala240Val VAR_016911 rs769894315

ClinVar genetic disease variations for 3-Methylglutaconic Aciduria, Type I:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 AUH NM_001698.2(AUH): c.589C> T (p.Arg197Ter) single nucleotide variant Pathogenic rs121434636 GRCh37 Chromosome 9, 94060275: 94060275
2 AUH NM_001698.2(AUH): c.895-1G> A single nucleotide variant Pathogenic rs730880309 GRCh37 Chromosome 9, 93978389: 93978389
3 AUH NM_001698.2(AUH): c.80delG (p.Ser27Metfs) deletion Pathogenic rs730880310 GRCh37 Chromosome 9, 94124092: 94124092
4 AUH NM_001698.2(AUH): c.263-2A> G single nucleotide variant Pathogenic rs730880311 GRCh37 Chromosome 9, 94118439: 94118439
5 AUH NM_001698.2(AUH): c.943-2A> G single nucleotide variant Pathogenic rs730880312 GRCh37 Chromosome 9, 93976709: 93976709
6 MT-TL1 m.3243A> G single nucleotide variant Pathogenic rs199474657 GRCh37 Chromosome MT, 3243: 3243
7 AUH NM_001698.2(AUH): c.559G> A (p.Gly187Ser) single nucleotide variant Pathogenic rs387906755 GRCh37 Chromosome 9, 94060305: 94060305
8 AUH NM_001698.2(AUH): c.650G> A (p.Gly217Asp) single nucleotide variant Pathogenic rs387906756 GRCh37 Chromosome 9, 94058308: 94058308
9 AUH NM_001698.2(AUH): c.991A> T (p.Lys331Ter) single nucleotide variant Pathogenic rs387906757 GRCh37 Chromosome 9, 93976659: 93976659
10 AUH NM_001698.2(AUH): c.373C> T (p.Arg125Trp) single nucleotide variant Likely pathogenic rs200030276 GRCh37 Chromosome 9, 94118210: 94118210

Expression for 3-Methylglutaconic Aciduria, Type I

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

Pathways for 3-Methylglutaconic Aciduria, Type I

GO Terms for 3-Methylglutaconic Aciduria, Type I

Cellular components related to 3-Methylglutaconic Aciduria, Type I according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 apical part of cell GO:0045177 9.32 AMN CUBN
2 clathrin-coated pit GO:0005905 9.26 AMN CUBN
3 endocytic vesicle GO:0030139 9.16 AMN CUBN
4 mitochondrion GO:0005739 9.02 AUH DNAJC19 EHHADH OPA3 SERAC1
5 brush border membrane GO:0031526 8.96 AMN CUBN

Biological processes related to 3-Methylglutaconic Aciduria, Type I according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.5 CUBN EHHADH SERAC1
2 fatty acid beta-oxidation GO:0006635 9.26 AUH EHHADH
3 cobalamin metabolic process GO:0009235 9.16 AMN CUBN
4 high-density lipoprotein particle clearance GO:0034384 8.96 AMN CUBN
5 cobalamin transport GO:0015889 8.62 AMN CUBN

Molecular functions related to 3-Methylglutaconic Aciduria, Type I according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 enoyl-CoA hydratase activity GO:0004300 8.62 AUH EHHADH

Sources for 3-Methylglutaconic Aciduria, Type I

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....