MCID: 3MT021
MIFTS: 27

3-Methylglutaconic Aciduria, Type Viii

Categories: Genetic diseases, Neuronal diseases, Metabolic diseases, Rare diseases, Eye diseases, Cardiovascular 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 6
Mgca8 57 75
3-Methylglutaconic Aciduria, Type Vii 75
3-Methylglutaconic Aciduria Type 8 59
3-Methylglutaconic Aciduria 8 75
Mga8 59

Characteristics:

OMIM:

57
Miscellaneous:
death in infancy
onset soon after birth

Inheritance:
autosomal recessive


HPO:

32
3-methylglutaconic aciduria, type viii:
Mortality/Aging death in infancy
Inheritance autosomal recessive inheritance


Classifications:



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)

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 cataract

UniProtKB/Swiss-Prot : 75 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 11.7
2 clpb deficiency 11.3
3 3-methylglutaconic aciduria 8.2 AUP1 HTRA2 LOXL3

Symptoms & Phenotypes for 3-Methylglutaconic Aciduria, Type Viii

Symptoms via clinical synopsis from OMIM:

57
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

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

32 (show all 19)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 32 occasional (7.5%) HP:0000407
2 cataract 32 HP:0000518
3 hypertonia 32 HP:0001276
4 generalized hypotonia 32 HP:0001290
5 dystonia 32 HP:0001332
6 tremor 32 HP:0001337
7 growth delay 32 HP:0001510
8 bradycardia 32 HP:0001662
9 neutropenia 32 HP:0001875
10 poor suck 32 HP:0002033
11 cerebral atrophy 32 HP:0002059
12 hypoplasia of the corpus callosum 32 HP:0002079
13 apnea 32 HP:0002104
14 ventriculomegaly 32 HP:0002119
15 increased serum lactate 32 HP:0002151
16 increased csf lactate 32 HP:0002490
17 respiratory failure 32 HP:0002878
18 3-methylglutaconic aciduria 32 HP:0003535
19 postnatal microcephaly 32 HP:0005484

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

26 (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 LOXL3 AUP1
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

Anatomical Context for 3-Methylglutaconic Aciduria, Type Viii

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

41
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:

75
# 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

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10 dbSNP
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17 ExPASy
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62 PubMed
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69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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