MGCA8
MCID: 3MT021
MIFTS: 29

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 58 30 6
Mgca8 58 76
3-Methylglutaconic Aciduria Type Viii, Mgca8 12
3-Methylglutaconic Aciduria, Type Vii 76
3-Methylglutaconic Aciduria Type Viii 12
3-Methylglutaconic Aciduria Type 8 60
3-Methylglutaconic Aciduria 8 76
Mga8 60

Characteristics:

OMIM:

58
Miscellaneous:
death in infancy
onset soon after birth

Inheritance:
autosomal recessive


HPO:

33
3-methylglutaconic aciduria, type viii:
Mortality/Aging death in infancy
Inheritance autosomal recessive inheritance


Classifications:



Summaries for 3-Methylglutaconic Aciduria, Type Viii

OMIM : 58 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)

MalaCards based summary : 3-Methylglutaconic Aciduria, Type Viii, also known as mgca8, is related to 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia and clpb deficiency. An important gene associated with 3-Methylglutaconic Aciduria, Type Viii is HTRA2 (HtrA Serine Peptidase 2). Affiliated tissues include brain, and related phenotypes are sensorineural hearing impairment and seizures

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

UniProtKB/Swiss-Prot : 76 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 family:

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

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 with cataracts, neurologic involvement, and neutropenia 11.9
2 clpb deficiency 11.4
3 3-methylglutaconic aciduria 9.6 HTRA2 LOXL3

Symptoms & Phenotypes for 3-Methylglutaconic Aciduria, Type Viii

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

33 (show all 20)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 33 occasional (7.5%) HP:0000407
2 seizures 33 HP:0001250
3 tremor 33 HP:0001337
4 cataract 33 HP:0000518
5 hypertonia 33 HP:0001276
6 growth delay 33 HP:0001510
7 dystonia 33 HP:0001332
8 apnea 33 HP:0002104
9 ventriculomegaly 33 HP:0002119
10 increased serum lactate 33 HP:0002151
11 respiratory failure 33 HP:0002878
12 neutropenia 33 HP:0001875
13 generalized hypotonia 33 HP:0001290
14 hypoplasia of the corpus callosum 33 HP:0002079
15 cerebral atrophy 33 HP:0002059
16 poor suck 33 HP:0002033
17 postnatal microcephaly 33 HP:0005484
18 increased csf lactate 33 HP:0002490
19 bradycardia 33 HP:0001662
20 3-methylglutaconic aciduria 33 HP:0003535

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
tremor
hypertonia
dystonia
cerebral atrophy
enlarged ventricles
more
Laboratory Abnormalities:
increased serum lactate
increased csf lactate
3-methylglutaconic aciduria

Immunology:
neutropenia

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

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

Abdomen Gastrointestinal:
feeding difficulties
poor suck

Respiratory:
respiratory failure
apneic episodes

Cardiovascular Heart:
bradycardia

Head And Neck Head:
microcephaly, postnatal

Growth Other:
poor growth

Clinical features from OMIM:

617248

GenomeRNAi Phenotypes related to 3-Methylglutaconic Aciduria, Type Viii according to GeneCards Suite gene sharing:

27 (show all 20)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-100 9.8 AUP1
2 Increased shRNA abundance (Z-score > 2) GR00366-A-124 9.8 LOXL3
3 Increased shRNA abundance (Z-score > 2) GR00366-A-128 9.8 LOXL3
4 Increased shRNA abundance (Z-score > 2) GR00366-A-13 9.8 LOXL3
5 Increased shRNA abundance (Z-score > 2) GR00366-A-149 9.8 LOXL3
6 Increased shRNA abundance (Z-score > 2) GR00366-A-161 9.8 AUP1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-163 9.8 AUP1
8 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.8 LOXL3
9 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.8 AUP1 LOXL3
10 Increased shRNA abundance (Z-score > 2) GR00366-A-35 9.8 AUP1 LOXL3
11 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.8 AUP1
12 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.8 LOXL3
13 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.8 AUP1
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-134 9.56 AUP1 LOXL3
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-150 9.56 AUP1
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-180 9.56 AUP1
17 Decreased shRNA abundance (Z-score < -2) GR00366-A-193 9.56 LOXL3
18 Decreased shRNA abundance (Z-score < -2) GR00366-A-212 9.56 AUP1
19 Decreased shRNA abundance (Z-score < -2) GR00366-A-55 9.56 AUP1
20 Decreased shRNA abundance (Z-score < -2) GR00366-A-71 9.56 AUP1

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 30 HTRA2

Anatomical Context for 3-Methylglutaconic Aciduria, Type Viii

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

42
Brain

Publications for 3-Methylglutaconic Aciduria, Type Viii

Variations for 3-Methylglutaconic Aciduria, Type Viii

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

76
# Symbol AA change Variation ID SNP ID
1 HTRA2 p.Arg404Gln VAR_077961 rs767006508

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

6
# Gene Variation Type Significance SNP ID Assembly Location
1 HTRA2 NM_013247.4(HTRA2): c.1211G> A (p.Arg404Gln) single nucleotide variant Pathogenic rs767006508 GRCh37 Chromosome 2, 74759841: 74759841
2 HTRA2 NM_013247.4(HTRA2): c.1211G> A (p.Arg404Gln) single nucleotide variant Pathogenic rs767006508 GRCh38 Chromosome 2, 74532714: 74532714
3 HTRA2 NM_013247.4(HTRA2): c.1316_1320delTGCAG (p.Val439Aspfs) deletion Pathogenic rs1057519080 GRCh37 Chromosome 2, 74760051: 74760055
4 HTRA2 NM_013247.4(HTRA2): c.1316_1320delTGCAG (p.Val439Aspfs) deletion Pathogenic rs1057519080 GRCh38 Chromosome 2, 74532924: 74532928
5 HTRA2 NM_013247.4(HTRA2): c.906+1G> C single nucleotide variant Pathogenic rs1057519081 GRCh38 Chromosome 2, 74531106: 74531106
6 HTRA2 NM_013247.4(HTRA2): c.906+1G> C single nucleotide variant Pathogenic rs1057519081 GRCh37 Chromosome 2, 74758233: 74758233
7 HTRA2 NM_013247.4(HTRA2): c.728_730delTGCinsCAT (p.Leu243_Pro244delinsProSer) indel Pathogenic rs1057519082 GRCh38 Chromosome 2, 74530927: 74530929
8 HTRA2 NM_013247.4(HTRA2): c.728_730delTGCinsCAT (p.Leu243_Pro244delinsProSer) indel Pathogenic rs1057519082 GRCh37 Chromosome 2, 74758054: 74758056

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
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
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43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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