MGCA4
MCID: 3MT019
MIFTS: 36

3-Methylglutaconic Aciduria, Type Iv (MGCA4)

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

Aliases & Classifications for 3-Methylglutaconic Aciduria, Type Iv

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

Name: 3-Methylglutaconic Aciduria, Type Iv 56 39
3-Methylglutaconic Aciduria Type 4 12 58 15 71
Mga4 56 12 58
3-Methylglutaconic Aciduria Type Iv 12 71
Mgca4 56 12
3 Alpha Methylglutaconic Aciduria Type Iv 52
Not Otherwise Specified 3-Mga-Uria Type 52
3 Methylglutaconic Aciduria Type Iv 52
Mga, Type Iv; Mga4 56
Mga, Type Iv 56
Mga Type Iv 12

Characteristics:

Orphanet epidemiological data:

58
3-methylglutaconic aciduria type 4
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive


HPO:

31
3-methylglutaconic aciduria, type iv:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare eye diseases
Inborn errors of metabolism


Summaries for 3-Methylglutaconic Aciduria, Type Iv

NIH Rare Diseases : 52 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. Visit the Orphanet disease page for more resources.

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 seizures

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

OMIM : 56 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)

Related Diseases for 3-Methylglutaconic Aciduria, Type Iv

Diseases in the 3-Methylglutaconic Aciduria, Type Iii family:

3-Methylglutaconic Aciduria, Type I 3-Methylglutaconic Aciduria, Type Iv
3-Methylglutaconic Aciduria, Type V 3-Methylglutaconic Aciduria, Type Vii
3-Methylglutaconic Aciduria, Type Viii 3-Methylglutaconic Aciduria, Type Ix
3-Methylglutaconic Aciduria

Diseases related to 3-Methylglutaconic Aciduria, Type Iv via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 23)
# Related Disease Score Top Affiliating Genes
1 3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome 31.9 TMEM70 SERAC1 OPA3 DARS2 AUH
2 3-methylglutaconic aciduria 29.9 TMEM70 SERAC1 OPA3 GGA2 AUH
3 branchiootic syndrome 1 10.4
4 central core disease of muscle 10.2
5 mitochondrial dna depletion syndrome 4a 10.2
6 leigh syndrome 10.2
7 mitochondrial complex v deficiency, nuclear type 1 10.2
8 dilated cardiomyopathy 10.2
9 methylmalonic acidemia 10.2
10 lactic acidosis 10.2
11 dystonia 10.2
12 clpb deficiency 10.2
13 encephalopathy 10.2
14 sengers syndrome 10.1 TMEM70 SERAC1
15 encephalopathy, ethylmalonic 10.0 TMEM70 NUDT16L1
16 barth syndrome 10.0 TMEM70 SERAC1
17 amino acid metabolic disorder 9.8 SERAC1 OPA3
18 3-methylglutaconic aciduria, type vii 9.7 GGA2 GGA1 FSBP
19 3-methylglutaconic aciduria, type v 9.6 TMEM70 SERAC1 OPA3 AUH
20 mitochondrial metabolism disease 9.5 TMEM70 SERAC1 OPA3 DARS2
21 organic acidemia 9.5 TMEM70 SERAC1 OPA3 AUH
22 3-methylglutaconic aciduria, type iii 9.0 TMEM70 SERAC1 OPA3 GGA2 DARS2 AUH
23 3-methylglutaconic aciduria, type i 7.6 TMEM70 SERAC1 OPA3 HPR GGA2 GGA1

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



Diseases related to 3-Methylglutaconic Aciduria, Type Iv

Symptoms & Phenotypes for 3-Methylglutaconic Aciduria, Type Iv

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

58 31 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 seizures 58 31 hallmark (90%) Very frequent (99-80%) HP:0001250
3 spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001257
4 failure to thrive 58 31 hallmark (90%) Very frequent (99-80%) HP:0001508
5 muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001252
6 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
7 3-methylglutaconic aciduria 58 31 hallmark (90%) Very frequent (99-80%) HP:0003535
8 dysgenesis of the cerebellar vermis 58 31 frequent (33%) Frequent (79-30%) HP:0002195
9 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000365
10 cataract 58 31 occasional (7.5%) Occasional (29-5%) HP:0000518
11 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
12 hypoglycemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001943
13 decreased liver function 58 31 occasional (7.5%) Occasional (29-5%) HP:0001410
14 cardiomyopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001638
15 thrombocytopenia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001873
16 lactic acidosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0003128
17 iris hypopigmentation 58 31 occasional (7.5%) Occasional (29-5%) HP:0007730
18 inguinal hernia 31 HP:0000023
19 cryptorchidism 31 HP:0000028
20 neonatal hypotonia 31 HP:0001319
21 areflexia 31 HP:0001284
22 severe global developmental delay 31 HP:0011344
23 neonatal respiratory distress 31 HP:0002643
24 cerebellar dysplasia 31 HP:0007033
25 single transverse palmar crease 31 HP:0000954
26 3-methylglutaric aciduria 31 HP:0003344
27 biventricular hypertrophy 31 HP:0200128
28 subvalvular aortic stenosis 31 HP:0001682

Symptoms via clinical synopsis from OMIM:

56
Abdomen:
inguinal hernia

Neuro:
neonatal hypotonia
severe psychomotor retardation
cerebellar dysgenesis
absent reflexes

Cardiac:
subaortic stenosis
biventricular hypertrophy

Lab:
3-methylglutaconicaciduria
3-methylglutaricaciduria

G U:
cryptorchidism

Resp:
neonatal respiratory distress

Skin:
simian crease

Clinical features from OMIM:

250951

Drugs & Therapeutics for 3-Methylglutaconic Aciduria, Type Iv

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

Genetic Tests for 3-Methylglutaconic Aciduria, Type Iv

Anatomical Context for 3-Methylglutaconic Aciduria, Type Iv

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

40
Eye, Liver

Publications for 3-Methylglutaconic Aciduria, Type Iv

Articles related to 3-Methylglutaconic Aciduria, Type Iv:

# Title Authors PMID Year
1
3-methylglutaconic aciduria type IV: a syndrome with an evolving phenotype. 61 56
21646875 2011
2
3-Methylglutaconic aciduria: a common biochemical marker in various syndromes with diverse clinical features. 56
15719488 2005
3
3-Methylglutaconic aciduria: a marker for as yet unspecified disorders and the relevance of prenatal diagnosis in a 'new' type ('type 4'). 56
1382150 1992
4
Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature: proper classification and nomenclature. 61
23296368 2013
5
Infantile mitochondrial hepatopathy is a cardinal feature of MEGDEL syndrome (3-methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy and Leigh-like syndrome) caused by novel mutations in SERAC1. 61
23918762 2013
6
Mild form of 3-methylglutaconic aciduria type IV and mutation in the TMEM70 genes. 61
23382305 2013
7
Biochemical and genetic analysis of 3-methylglutaconic aciduria type IV: a diagnostic strategy. 61
19015156 2009
8
3-methylglutaconic aciduria type 4 manifesting as Leigh syndrome in 2 siblings. 61
17621487 2007

Variations for 3-Methylglutaconic Aciduria, Type Iv

Expression for 3-Methylglutaconic Aciduria, Type Iv

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

Pathways for 3-Methylglutaconic Aciduria, Type Iv

Pathways related to 3-Methylglutaconic Aciduria, Type Iv according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.22 GGA3 GGA2 GGA1
2 10.47 GGA3 GGA2 GGA1

GO Terms for 3-Methylglutaconic Aciduria, Type Iv

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

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.55 TMEM70 SERAC1 OPA3 DARS2 AUH
2 endosome membrane GO:0010008 9.13 GGA3 GGA2 GGA1
3 early endosome membrane GO:0031901 8.8 GGA3 GGA2 GGA1

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

# Name GO ID Score Top Affiliating Genes
1 intracellular protein transport GO:0006886 9.5 GGA3 GGA2 GGA1
2 vesicle-mediated transport GO:0016192 9.43 GGA3 GGA2 GGA1
3 positive regulation of protein catabolic process GO:0045732 9.37 GGA3 GGA1
4 cellular protein metabolic process GO:0044267 9.33 GGA3 GGA2 GGA1
5 Golgi to plasma membrane protein transport GO:0043001 9.13 GGA3 GGA2 GGA1
6 protein localization to cell surface GO:0034394 8.8 GGA3 GGA2 GGA1

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

# Name GO ID Score Top Affiliating Genes
1 ADP-ribosylation factor binding GO:0030306 8.8 GGA3 GGA2 GGA1

Sources for 3-Methylglutaconic Aciduria, Type Iv

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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