MGCA8
MCID: 3MT021
MIFTS: 28

3-Methylglutaconic Aciduria, Type Viii (MGCA8)

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

Aliases & Classifications for 3-Methylglutaconic Aciduria, Type Viii

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

Name: 3-Methylglutaconic Aciduria, Type Viii 57 29 6
3-Methylglutaconic Aciduria Type 8 12 58
Mgca8 57 72
3-Methylglutaconic Aciduria Type Viii, Mgca8 12
3-Methylglutaconic Aciduria, Type Vii 72
3-Methylglutaconic Aciduria 8 72
Mga8 58

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
death in infancy
onset soon after birth

Inheritance:
autosomal recessive


HPO:

31
3-methylglutaconic aciduria, type viii:
Onset and clinical course death in infancy
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for 3-Methylglutaconic Aciduria, Type Viii

OMIM® : 57 MGCA8 is an autosomal recessive metabolic disorder resulting in death in infancy. Features include hypotonia, abnormal movements, respiratory insufficiency with apneic episodes, and lack of developmental progress, often with seizures. Brain imaging is variable, but may show progressive cerebral atrophy. Laboratory studies show increased serum lactate and 3-methylglutaconic aciduria, suggesting a mitochondrial defect (summary by Mandel et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950). (617248) (Updated 20-May-2021)

MalaCards based summary : 3-Methylglutaconic Aciduria, Type Viii, also known as 3-methylglutaconic aciduria type 8, is related to 3-methylglutaconic aciduria and 3-methylglutaconic aciduria, type vii. An important gene associated with 3-Methylglutaconic Aciduria, Type Viii is HTRA2 (HtrA Serine Peptidase 2). Affiliated tissues include eye, and related phenotypes are sensorineural hearing impairment and tremor

Disease Ontology : 12 A 3-methylglutaconic aciduria that has material basis in homozygous mutation in the HTRA2 gene on chromosome 2p13.

UniProtKB/Swiss-Prot : 72 3-methylglutaconic aciduria 8: An autosomal recessive inborn error of metabolism resulting in early death. Clinical features include extreme hypertonia observed at birth, alternating with hypotonia, subsequent appearance of extrapyramidal symptoms, lack of psychomotor development, microcephaly, and intractable seizures. Patients show lactic acidemia, 3- methylglutaconic aciduria, intermittent neutropenia, and progressive brain atrophy.

Related Diseases for 3-Methylglutaconic Aciduria, Type Viii

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 Viii via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 3-methylglutaconic aciduria 29.6 LOXL3 HTRA2
2 3-methylglutaconic aciduria, type vii 11.9
3 clpb deficiency 11.5
4 respiratory failure 10.2
5 neutropenia 10.2
6 encephalopathy 10.2
7 hypertonia 10.2
8 hypotonia 10.2

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



Diseases related to 3-Methylglutaconic Aciduria, Type Viii

Symptoms & Phenotypes for 3-Methylglutaconic Aciduria, Type Viii

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

31 (show all 20)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 31 occasional (7.5%) HP:0000407
2 tremor 31 HP:0001337
3 cataract 31 HP:0000518
4 hypertonia 31 HP:0001276
5 growth delay 31 HP:0001510
6 ventriculomegaly 31 HP:0002119
7 increased serum lactate 31 HP:0002151
8 apnea 31 HP:0002104
9 dystonia 31 HP:0001332
10 neutropenia 31 HP:0001875
11 respiratory failure 31 HP:0002878
12 hypoplasia of the corpus callosum 31 HP:0002079
13 increased csf lactate 31 HP:0002490
14 poor suck 31 HP:0002033
15 cerebral atrophy 31 HP:0002059
16 postnatal microcephaly 31 HP:0005484
17 generalized hypotonia 31 HP:0001290
18 3-methylglutaconic aciduria 31 HP:0003535
19 bradycardia 31 HP:0001662
20 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
tremor
hypertonia
dystonia
cerebral atrophy
enlarged ventricles
more
Immunology:
neutropenia

Abdomen Gastrointestinal:
feeding difficulties
poor suck

Muscle Soft Tissue:
hypotonia
abnormal mitochondria seen on muscle biopsy (in some patients)
irregular cristae
disordered myofilaments
immature muscle fibers
more
Head And Neck Eyes:
cataracts
lack of vision

Growth Other:
poor growth

Laboratory Abnormalities:
increased serum lactate
increased csf lactate
3-methylglutaconic aciduria

Respiratory:
respiratory failure
apneic episodes

Cardiovascular Heart:
bradycardia

Head And Neck Head:
microcephaly, postnatal

Head And Neck Ears:
sensorineural deafness (in some patients)

Clinical features from OMIM®:

617248 (Updated 20-May-2021)

Drugs & Therapeutics for 3-Methylglutaconic Aciduria, Type Viii

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

Genetic Tests for 3-Methylglutaconic Aciduria, Type Viii

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

# Genetic test Affiliating Genes
1 3-Methylglutaconic Aciduria, Type Viii 29 HTRA2

Anatomical Context for 3-Methylglutaconic Aciduria, Type Viii

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

40
Eye

Publications for 3-Methylglutaconic Aciduria, Type Viii

Articles related to 3-Methylglutaconic Aciduria, Type Viii:

# Title Authors PMID Year
1
Pathogenic variants in HTRA2 cause an early-onset mitochondrial syndrome associated with 3-methylglutaconic aciduria. 57 6
27696117 2017
2
Deficiency of HTRA2/Omi is associated with infantile neurodegeneration and 3-methylglutaconic aciduria. 57 6
27208207 2016
3
3-Methylglutaconic aciduria type VIII in an Indian neonate. 61
32445293 2020

Variations for 3-Methylglutaconic Aciduria, Type Viii

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

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HTRA2 NM_145074.2(HTRA2):c.711+106_711+108delinsCAT Indel Pathogenic 372212 rs1057519082 GRCh37: 2:74758054-74758056
GRCh38: 2:74530927-74530929
2 HTRA2 , LOXL3 NM_032603.5(LOXL3):c.*682_*686del Deletion Pathogenic 372210 rs1057519080 GRCh37: 2:74760047-74760051
GRCh38: 2:74532920-74532924
3 HTRA2 NM_013247.4(HTRA2):c.906+1G>C SNV Pathogenic 372211 rs1057519081 GRCh37: 2:74758233-74758233
GRCh38: 2:74531106-74531106
4 HTRA2 , LOXL3 NM_032603.5(LOXL3):c.*892C>T SNV Pathogenic 372209 rs767006508 GRCh37: 2:74759841-74759841
GRCh38: 2:74532714-74532714
5 HTRA2 NM_013247.5(HTRA2):c.739C>T (p.Arg247Cys) SNV Uncertain significance 973448 GRCh37: 2:74758065-74758065
GRCh38: 2:74530938-74530938
6 HTRA2 NM_013247.5(HTRA2):c.146G>C (p.Arg49Pro) SNV Uncertain significance 1027794 GRCh37: 2:74757279-74757279
GRCh38: 2:74530152-74530152

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

72
# Symbol AA change Variation ID SNP ID
1 HTRA2 p.Arg404Gln VAR_077961 rs767006508

Expression for 3-Methylglutaconic Aciduria, Type Viii

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

Pathways for 3-Methylglutaconic Aciduria, Type Viii

GO Terms for 3-Methylglutaconic Aciduria, Type Viii

Sources for 3-Methylglutaconic Aciduria, Type Viii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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