MC4DN6
MCID: MTC209
MIFTS: 24

Mitochondrial Complex Iv Deficiency, Nuclear Type 6 (MC4DN6)

Categories: Cardiovascular diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Respiratory diseases

Aliases & Classifications for Mitochondrial Complex Iv Deficiency, Nuclear Type 6

MalaCards integrated aliases for Mitochondrial Complex Iv Deficiency, Nuclear Type 6:

Name: Mitochondrial Complex Iv Deficiency, Nuclear Type 6 57
Cardioencephalomyopathy, Fatal Infantile, Due to Cytochrome C Oxidase Deficiency 2 57 72 29 13 6 70
Cemcox2 57 72
Cardioencephalomyopathy, Fatal Infantile, Due to Cytochrome C Oxidase Deficiency 2; Cemcox2 57
Cardioencephalomyopathy, Fatal Infantile, Due to Cytochrome C Oxidase Deficiency, Type 2 39
Fatal Infantile Cardioencephalomyopathy Due to Cytochrome C Oxidase Deficiency 2 12
Mc4dn6 57

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
onset in infancy (range neonatal to 7 months)


HPO:

31
mitochondrial complex iv deficiency, nuclear type 6:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0080358
OMIM® 57 615119
OMIM Phenotypic Series 57 PS220110
UMLS 70 C3554534

Summaries for Mitochondrial Complex Iv Deficiency, Nuclear Type 6

OMIM® : 57 Mitochondrial complex IV deficiency nuclear type 6 (MC4DN6) is an autosomal recessive multisystem metabolic disorder with a highly variable phenotype. Some patients present in the neonatal period with encephalomyopathic features, whereas others present later in the first year of life with developmental regression. Manifestations include hypotonia, feeding difficulties, and global developmental delay. Many, but not all, patients develop hypertrophic cardiomyopathy, which may result in early death. Additional more variable features may include poor overall growth, microcephaly, seizures, neurodegeneration, spasticity, visual defects, retinopathy, and hepatic steatosis. Brain imaging in some patients shows features consistent with Leigh syndrome (see 256000). Laboratory studies show increased serum lactate and decreased levels and activity of mitochondrial respiratory complex IV (summary by Kennaway et al., 1990 and Oquendo et al., 2004). For a discussion of genetic heterogeneity of mitochondrial complex IV (cytochrome c oxidase) deficiency, see 220110. (615119) (Updated 05-Apr-2021)

MalaCards based summary : Mitochondrial Complex Iv Deficiency, Nuclear Type 6, is also known as cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2. An important gene associated with Mitochondrial Complex Iv Deficiency, Nuclear Type 6 is COX15 (Cytochrome C Oxidase Assembly Homolog COX15). Affiliated tissues include skeletal muscle, and related phenotypes are microcephaly and hepatic steatosis

Disease Ontology : 12 A fatal infantile cardioencephalomyopathy due to cytochrome c oxidase deficiency that has material basis in compound heterozygous mutation in the COX15 gene on chromosome 10q24.

UniProtKB/Swiss-Prot : 72 Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2: An infantile disorder, with a rapidly progressive fatal course, characterized by cytochrome c oxidase deficiency. Clinical features include microcephaly, encephalopathy, hypertrophic cardiomyopathy, persistent lactic acidosis, respiratory distress, hypotonia and seizures. Postmortem cardiac muscle studies show marked complex IV deficiency. Complex IV activity is only slightly decreased in the skeletal muscle.

Related Diseases for Mitochondrial Complex Iv Deficiency, Nuclear Type 6

Symptoms & Phenotypes for Mitochondrial Complex Iv Deficiency, Nuclear Type 6

Human phenotypes related to Mitochondrial Complex Iv Deficiency, Nuclear Type 6:

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 microcephaly 31 HP:0000252
2 hepatic steatosis 31 HP:0001397
3 decreased fetal movement 31 HP:0001558
4 encephalopathy 31 HP:0001298
5 cardiomyopathy 31 HP:0001638
6 generalized hypotonia 31 HP:0001290
7 gliosis 31 HP:0002171

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
spasticity
developmental regression
global developmental delay
dystonia
encephalopathy
more
Head And Neck Head:
microcephaly

Abdomen Gastrointestinal:
poor feeding

Prenatal Manifestations Movement:
decreased fetal movements

Cardiovascular Heart:
hypertrophic cardiomyopathy, biventricular (in some patients)
glycogen deposition
markedly decreased cytochrome c oxidase activity

Metabolic Features:
lactic acidosis, persistent

Muscle Soft Tissue:
muscle weakness
increased intermyofibrillar and subsarcolemmal glycogen
mildly decreased cytochrome c oxidase activity

Head And Neck Eyes:
visual impairment
retinopathy (in some patients)

Growth Other:
poor overall growth

Laboratory Abnormalities:
increased serum and csf lactate
mitochondrial respiratory complex iv deficiency in patient tissues

Abdomen Liver:
steatosis (rare)

Clinical features from OMIM®:

615119 (Updated 05-Apr-2021)

Drugs & Therapeutics for Mitochondrial Complex Iv Deficiency, Nuclear Type 6

Search Clinical Trials , NIH Clinical Center for Mitochondrial Complex Iv Deficiency, Nuclear Type 6

Genetic Tests for Mitochondrial Complex Iv Deficiency, Nuclear Type 6

Genetic tests related to Mitochondrial Complex Iv Deficiency, Nuclear Type 6:

# Genetic test Affiliating Genes
1 Cardioencephalomyopathy, Fatal Infantile, Due to Cytochrome C Oxidase Deficiency 2 29 COX15

Anatomical Context for Mitochondrial Complex Iv Deficiency, Nuclear Type 6

MalaCards organs/tissues related to Mitochondrial Complex Iv Deficiency, Nuclear Type 6:

40
Skeletal Muscle

Publications for Mitochondrial Complex Iv Deficiency, Nuclear Type 6

Articles related to Mitochondrial Complex Iv Deficiency, Nuclear Type 6:

# Title Authors PMID Year
1
Infantile cardioencephalopathy due to a COX15 gene defect: report and review. 57 6
21412973 2011
2
Novel mutations in COX15 in a long surviving Leigh syndrome patient with cytochrome c oxidase deficiency. 57 6
15863660 2005
3
Functional and genetic studies demonstrate that mutation in the COX15 gene can cause Leigh syndrome. 57 6
15235026 2004
4
Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy. 6 57
12474143 2003
5
Isoforms of mammalian cytochrome c oxidase: correlation with human cytochrome c oxidase deficiency. 57 6
2175025 1990

Variations for Mitochondrial Complex Iv Deficiency, Nuclear Type 6

ClinVar genetic disease variations for Mitochondrial Complex Iv Deficiency, Nuclear Type 6:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 COX15 NM_078470.6(COX15):c.396-3C>G SNV Pathogenic 280009 rs200910834 GRCh37: 10:101486914-101486914
GRCh38: 10:99727157-99727157
2 COX15 NM_078470.6(COX15):c.1030T>C (p.Ser344Pro) SNV Pathogenic 40258 rs397514662 GRCh37: 10:101476176-101476176
GRCh38: 10:99716419-99716419
3 COX15 NM_078470.6(COX15):c.452C>G (p.Ser151Ter) SNV Pathogenic 496238 rs149718203 GRCh37: 10:101486855-101486855
GRCh38: 10:99727098-99727098
4 COX15 NM_078470.6(COX15):c.649C>T (p.Arg217Trp) SNV Pathogenic 6175 rs28939711 GRCh37: 10:101483814-101483814
GRCh38: 10:99724057-99724057
5 COX15 NM_078470.6(COX15):c.305G>A (p.Trp102Ter) SNV Pathogenic 1029833 GRCh37: 10:101487288-101487288
GRCh38: 10:99727531-99727531
6 COX15 NM_078470.6(COX15):c.1015G>A (p.Val339Met) SNV Uncertain significance 214252 rs141830307 GRCh37: 10:101476191-101476191
GRCh38: 10:99716434-99716434
7 COX15 NM_078470.6(COX15):c.532C>T (p.Arg178Cys) SNV Uncertain significance 522748 rs192078749 GRCh37: 10:101486775-101486775
GRCh38: 10:99727018-99727018
8 COX15 NM_078470.6(COX15):c.1209T>C (p.Asn403=) SNV Benign 137014 rs34652235 GRCh37: 10:101474368-101474368
GRCh38: 10:99714611-99714611
9 COX15 NM_078470.6(COX15):c.548G>A (p.Arg183His) SNV Benign 137016 rs35483721 GRCh37: 10:101486759-101486759
GRCh38: 10:99727002-99727002

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Complex Iv Deficiency, Nuclear Type 6:

72
# Symbol AA change Variation ID SNP ID
1 COX15 p.Arg217Trp VAR_019596 rs28939711

Expression for Mitochondrial Complex Iv Deficiency, Nuclear Type 6

Search GEO for disease gene expression data for Mitochondrial Complex Iv Deficiency, Nuclear Type 6.

Pathways for Mitochondrial Complex Iv Deficiency, Nuclear Type 6

GO Terms for Mitochondrial Complex Iv Deficiency, Nuclear Type 6

Sources for Mitochondrial Complex Iv Deficiency, Nuclear Type 6

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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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