COXPD8
MCID: CMB019
MIFTS: 26

Combined Oxidative Phosphorylation Deficiency 8 (COXPD8)

Categories: Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency 8

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency 8:

Name: Combined Oxidative Phosphorylation Deficiency 8 56 12 73 29 13 6 71
Coxpd8 56 12 58 73
Cardiomyopathy, Hypertrophic Mitochondrial, Fatal Infantile 56
Cardiomyopathy Hypertrophic Mitochondrial Fatal Infantile 73
Combined Oxidative Phosphorylation Deficiency, Type 8 39
Combined Oxidative Phosphorylation Defect Type 8 58

Characteristics:

Orphanet epidemiological data:

58
combined oxidative phosphorylation defect type 8
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: infantile;

OMIM:

56
Miscellaneous:
death in infancy

Inheritance:
autosomal recessive


HPO:

31
combined oxidative phosphorylation deficiency 8:
Clinical modifier death in infancy
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0111479
OMIM 56 614096
OMIM Phenotypic Series 56 PS609060
ICD10 via Orphanet 33 E88.8
Orphanet 58 ORPHA319504
MedGen 41 C3279793
UMLS 71 C3279793

Summaries for Combined Oxidative Phosphorylation Deficiency 8

OMIM : 56 COXPD8 is an autosomal recessive disorder due to dysfunction of the mitochondrial respiratory chain. The main clinical manifestation is a lethal infantile hypertrophic cardiomyopathy, but there may also be subtle skeletal muscle and brain involvement. Biochemical studies show combined respiratory chain complex deficiencies in complexes I, III, and IV in cardiac muscle, skeletal muscle, and brain. The liver is not affected (summary by Gotz et al., 2011). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). (614096)

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency 8, is also known as coxpd8, and has symptoms including generalized muscle weakness and staring spells. An important gene associated with Combined Oxidative Phosphorylation Deficiency 8 is AARS2 (Alanyl-TRNA Synthetase 2, Mitochondrial). Affiliated tissues include brain, skeletal muscle and liver, and related phenotypes are failure to thrive and eeg abnormality

Disease Ontology : 12 A combined oxidative phosphorylation deficiency characterized by lethal infantile hypertrophic cardiomyopathy and in some cases subtle skeletal muscle and brain involvement that has material basis in homozygous or compound heterozygous mutation in AARS2 on chromosome 6p21.1.

UniProtKB/Swiss-Prot : 73 Combined oxidative phosphorylation deficiency 8: A mitochondrial disease characterized by a lethal infantile hypertrophic cardiomyopathy, generalized muscle dysfunction and some neurologic involvement. The liver is not affected.

Related Diseases for Combined Oxidative Phosphorylation Deficiency 8

Symptoms & Phenotypes for Combined Oxidative Phosphorylation Deficiency 8

Human phenotypes related to Combined Oxidative Phosphorylation Deficiency 8:

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 31 HP:0001508
2 eeg abnormality 31 HP:0002353
3 hypertrophic cardiomyopathy 31 HP:0001639
4 generalized muscle weakness 31 HP:0003324
5 increased serum lactate 31 HP:0002151
6 lactic acidosis 31 HP:0003128
7 pulmonary hypoplasia 31 HP:0002089

Symptoms via clinical synopsis from OMIM:

56
Growth Other:
failure to thrive

Muscle Soft Tissue:
generalized muscle weakness

Metabolic Features:
lactic acidosis

Respiratory Lung:
pulmonary hypoplasia, mild

Cardiovascular Heart:
hypertrophic cardiomyopathy
histiocytoid changes

Laboratory Abnormalities:
increased serum lactate
decreased mitochondrial respiratory complexes i, iii, and iv in brain, heart, and skeletal muscle

Neurologic Central Nervous System:
staring spells
eeg abnormalities
periodic stiffness

Clinical features from OMIM:

614096

UMLS symptoms related to Combined Oxidative Phosphorylation Deficiency 8:


generalized muscle weakness, staring spells

Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency 8

Search Clinical Trials , NIH Clinical Center for Combined Oxidative Phosphorylation Deficiency 8

Genetic Tests for Combined Oxidative Phosphorylation Deficiency 8

Genetic tests related to Combined Oxidative Phosphorylation Deficiency 8:

# Genetic test Affiliating Genes
1 Combined Oxidative Phosphorylation Deficiency 8 29

Anatomical Context for Combined Oxidative Phosphorylation Deficiency 8

MalaCards organs/tissues related to Combined Oxidative Phosphorylation Deficiency 8:

40
Brain, Skeletal Muscle, Liver, Heart

Publications for Combined Oxidative Phosphorylation Deficiency 8

Articles related to Combined Oxidative Phosphorylation Deficiency 8:

# Title Authors PMID Year
1
Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. 56 6
25058219 2014
2
Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy. 56 6
21549344 2011
3
Novel (ovario) leukodystrophy related to AARS2 mutations. 6
24808023 2014
4
Retinopathy and optic atrophy: Expanding the phenotypic spectrum of pathogenic variants in the AARS2 gene. 61
28820624 2018

Variations for Combined Oxidative Phosphorylation Deficiency 8

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 8:

6 (show all 14) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 AARS2 NM_020745.4(AARS2):c.464T>G (p.Leu155Arg)SNV Pathogenic 30941 rs387907061 6:44279244-44279244 6:44311507-44311507
2 AARS2 NM_020745.4(AARS2):c.647dup (p.Cys218fs)duplication Pathogenic 143044 rs587777589 6:44278832-44278833 6:44311095-44311096
3 AARS2 NM_020745.4(AARS2):c.1561C>T (p.Arg521Ter)SNV Pathogenic 143046 rs587777591 6:44272809-44272809 6:44305072-44305072
4 AARS2 NM_020745.4(AARS2):c.2356G>A (p.Ala786Thr)SNV Pathogenic 488461 rs1554147776 6:44270547-44270547 6:44302810-44302810
5 AARS2 NM_020745.4(AARS2):c.2027A>C (p.Gln676Pro)SNV Pathogenic 623387 rs1561938413 6:44271141-44271141 6:44303404-44303404
6 AARS2 NM_020745.4(AARS2):c.1774C>T (p.Arg592Trp)SNV Pathogenic/Likely pathogenic 30940 rs138119149 6:44272249-44272249 6:44304512-44304512
7 AARS2 NM_020745.4(AARS2):c.2531T>C (p.Leu844Pro)SNV Likely pathogenic 807356 6:44269864-44269864 6:44302127-44302127
8 AARS2 NM_020745.4(AARS2):c.1534G>C (p.Asp512His)SNV Conflicting interpretations of pathogenicity 357070 rs146512155 6:44272836-44272836 6:44305099-44305099
9 AARS2 NM_020745.4(AARS2):c.985C>T (p.Arg329Cys)SNV Conflicting interpretations of pathogenicity 357074 rs200187887 6:44275041-44275041 6:44307304-44307304
10 AARS2 NM_020745.4(AARS2):c.1660C>T (p.Arg554Cys)SNV Uncertain significance 203376 rs146924860 6:44272474-44272474 6:44304737-44304737
11 AARS2 NM_020745.4(AARS2):c.1387C>T (p.Gln463Ter)SNV Uncertain significance 632486 rs1561940254 6:44273437-44273437 6:44305700-44305700
12 AARS2 NM_020745.4(AARS2):c.2683-1G>TSNV Uncertain significance 632485 rs374185049 6:44269004-44269004 6:44301267-44301267
13 AARS2 NM_020745.4(AARS2):c.1040+1G>ASNV Uncertain significance 632487 rs1561941287 6:44274985-44274985 6:44307248-44307248
14 AARS2 NM_020745.4(AARS2):c.2607G>A (p.Lys869=)SNV Benign 357059 rs498512 6:44269193-44269193 6:44301456-44301456

UniProtKB/Swiss-Prot genetic disease variations for Combined Oxidative Phosphorylation Deficiency 8:

73
# Symbol AA change Variation ID SNP ID
1 AARS2 p.Leu155Arg VAR_065956 rs387907061
2 AARS2 p.Arg592Trp VAR_065957 rs138119149

Expression for Combined Oxidative Phosphorylation Deficiency 8

Search GEO for disease gene expression data for Combined Oxidative Phosphorylation Deficiency 8.

Pathways for Combined Oxidative Phosphorylation Deficiency 8

GO Terms for Combined Oxidative Phosphorylation Deficiency 8

Sources for Combined Oxidative Phosphorylation Deficiency 8

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68 SNOMED-CT via HPO
69 TGDB
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72 UMLS via Orphanet
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