MCID: 3MT015
MIFTS: 44

3-Methylglutaconic Aciduria, Type I

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

Aliases & Classifications for 3-Methylglutaconic Aciduria, Type I

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

Name: 3-Methylglutaconic Aciduria, Type I 53 24 13
3-Methylglutaconyl-Coa Hydratase Deficiency 53 12 49 24 55 71
Mga1 53 12 24 55 71
3-Methylglutaconic Aciduria Type 1 12 55 14 69
3mg-Coa Hydratase Deficiency 12 55 71
Mga Type I 12 49 71
Mgca1 53 24 71
3 Methylglutaconyl Coa Hydratase Deficiency 72 49
3-Mg-Coa-Hydratase Deficiency 53 24
Mga, Type I 53 24
Megaloblastic Anemia Due to Inborn Errors of Metabolism 69
3-Alpha-Methylglutaconyl-Coa Hydratase Deficiency 71
3 Alpha Methylglutaconic Aciduria Type I 49
3-Alpha-Methylglutaconic Aciduria Type 1 71
3-@methylglutaconic Aciduria, Type I 69
Primary 3-Methylglutaconic Aciduria 24
3-Methylglutaconic Aciduria Type I 12
3 Methylglutaconic Aciduria Type 1 49
3-Methylglutaconic Aciduria 1 71
3mg Coa Hydratase Deficiency 49
Mga, Type I; Mga1 53
3-Mgca Type I 49
Auh Defect 24

Characteristics:

Orphanet epidemiological data:

55
3-methylglutaconic aciduria type 1
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
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:

31
3-methylglutaconic aciduria, type i:
Onset and clinical course phenotypic variability infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Inborn errors of metabolism


Summaries for 3-Methylglutaconic Aciduria, Type I

NIH Rare Diseases : 49 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 1 and megaloblastic anemia, and has symptoms including seizures, dystonia and failure to thrive. 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.

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

Genetics Home Reference : 24 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 : 53 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 : 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).

Wikipedia : 72 3-Methylglutaconic aciduria (MGA) is any of at least five metabolic disorders that impair the body\'s... more...

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:

53
Neurologic Central Nervous System:
cerebellar ataxia
athetosis
dystonia
dysarthria
hyperreflexia
more
Head And Neck Eyes:
optic atrophy

Genitourinary Bladder:
urinary incontinence (adult)

Growth Other:
failure to thrive

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:

55 31 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 55 31 occasional (7.5%) Occasional (29-5%) HP:0001250
2 dystonia 55 31 occasional (7.5%) Occasional (29-5%) HP:0001332
3 failure to thrive 55 31 hallmark (90%) Very frequent (99-80%) HP:0001508
4 global developmental delay 55 31 occasional (7.5%) Frequent (79-30%) HP:0001263
5 hepatomegaly 55 31 occasional (7.5%) Occasional (29-5%) HP:0002240
6 delayed speech and language development 55 31 frequent (33%) Frequent (79-30%) HP:0000750
7 microcephaly 55 31 occasional (7.5%) Occasional (29-5%) HP:0000252
8 hypoglycemia 55 31 occasional (7.5%) Occasional (29-5%) HP:0001943
9 coma 55 31 occasional (7.5%) Occasional (29-5%) HP:0001259
10 spastic tetraparesis 55 31 occasional (7.5%) Occasional (29-5%) HP:0001285
11 progressive cerebellar ataxia 55 31 occasional (7.5%) Occasional (29-5%) HP:0002073
12 3-methylglutaconic aciduria 55 31 hallmark (90%) Very frequent (99-80%) HP:0003535
13 abnormality of the basal ganglia 55 31 occasional (7.5%) Occasional (29-5%) HP:0002134
14 ataxia 31 HP:0001251
15 athetosis 31 HP:0002305
16 dysarthria 31 HP:0001260
17 hyperreflexia 31 HP:0001347
18 optic atrophy 31 HP:0000648
19 cognitive impairment 31 HP:0100543
20 spastic tetraplegia 31 HP:0002510
21 febrile seizures 31 HP:0002373
22 metabolic acidosis 31 HP:0001942
23 motor delay 31 HP:0001270
24 cerebral atrophy 31 HP:0002059
25 urinary incontinence 31 HP:0000020
26 short attention span 31 HP:0000736
27 leukoencephalopathy 31 HP:0002352

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


cerebellar ataxia, athetosis

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

Anatomical Context for 3-Methylglutaconic Aciduria, Type I

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

38
Brain, Eye, Skin

Publications for 3-Methylglutaconic Aciduria, Type I

Articles related to 3-Methylglutaconic Aciduria, Type I:

(show all 12)
# 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
3-methylglutaconic aciduria type I in a boy with fever-associated seizures. ( 15033206 )
2004
7
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
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-Methylglutaconyl-CoA hydratase deficiency: a new patient with speech retardation as the leading sign. ( 10896289 )
2000
11
3-Methylglutaconic aciduria type I: clinical heterogeneity as a neurometabolic disease. ( 10070612 )
1999
12
[3-Methylglutaconyl-CoA hydratase deficiency]. ( 9590049 )
1998

Variations for 3-Methylglutaconic Aciduria, Type I

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

71
# 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
# 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:

# 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 TMEM70
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:

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

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

# 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
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 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....