Combined oxidative phosphorylation defect type 4

General Information (adopted from Orphanet):

Synonyms, Signs: COXPD4
Number of Symptoms 26
OrphanetNr: 254925
OMIM Id: 610678
ICD-10: E88.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
Monogenic
17160893 [IBIS]
Age of onset: Neonatal
17160893 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Mitochondrial disorder due to a defect in mitochondrial protein synthesis
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease

Comment:

TUFM (= COXPD4, EFTU) is a mitochondrial protein that potently associates with NLR X1, and ATg12–ATg5 and ATg16L1. TUFM is known to be important in mitochondrial protein elongation. Overexpression and RNA interference targeting TUFM showed that the protein substantially inhibits RLR activation/type I IFN production, but augments autophagy (PMID:23321557). A mutation in the mitochondrial elongation factor Tu (EFTu) is described in Valente et al. (2007). A G-A transition at np 1016 of the cDNA converts the R residue at position 339 into a Q residue (R339Q) (PMID:17160893).

Symptom Information: Sort by abundance 

1
(HPO:0002013) Vomiting 17160893 IBIS 191 / 7739
2
(HPO:0000639) Nystagmus 17160893 IBIS 555 / 7739
3
(HPO:0002098) Respiratory distress 17160893 IBIS 75 / 7739
4
(HPO:0003128) Lactic acidosis 17160893 IBIS 116 / 7739
5
(HPO:0001942) Metabolic acidosis 17160893 IBIS 81 / 7739
6
(HPO:0001063) Acrocyanosis 17160893 IBIS 56 / 7739
7
(HPO:0011923) Decreased activity of mitochondrial complex I 17160893 IBIS 35 / 7739
8
(HPO:0008347) Decreased activity of mitochondrial complex IV 17160893 IBIS 31 / 7739
9
(HPO:0001987) Hyperammonemia 17160893 IBIS 50 / 7739
10
(HPO:0008935) Generalized neonatal hypotonia 17160893 IBIS 9 / 7739
11
(HPO:0001276) Hypertonia 17160893 IBIS 317 / 7739
12
(HPO:0001257) Spasticity 17160893 IBIS 251 / 7739
13
(HPO:0002179) Opisthotonus 17160893 IBIS 35 / 7739
14
(HPO:0002376) Developmental regression 17160893 IBIS 74 / 7739
15
(HPO:0001254) Lethargy 17160893 IBIS 104 / 7739
16
(HPO:0000252) Microcephaly 17160893 IBIS 832 / 7739
17
(HPO:0002240) Hepatomegaly 17160893 IBIS 467 / 7739
18
(HPO:0000980) Pallor 17160893 IBIS 52 / 7739
19
(HPO:0002134) Abnormality of the basal ganglia 17160893 IBIS 13 / 7739
20
(HPO:0002500) Abnormality of the cerebral white matter 17160893 IBIS 73 / 7739
21
(HPO:0001522) Death in infancy 17160893 IBIS 275 / 7739
22
(HPO:0002126) Polymicrogyria 17160893 IBIS 64 / 7739
23
(OMIM) Elevated serum glutamic oxaloacetic transaminase (SGOT) 17160893 IBIS 2 / 7739
24
(OMIM) Elevated serum glutamic pyruvic transaminase (SGPT) 17160893 IBIS 2 / 7739
25
(OMIM) Mildly elevated transaminases 17160893 IBIS 2 / 7739
26
(OMIM) Myocardial ischemia 17160893 IBIS 2 / 7739

Associated genes:

TUFM;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Valente et al. (2007) described 2 infants with neonatal lactic acidosis, rapidly progressive encephalopathy, severely decreased mitochondrial protein synthesis, and combined deficiency of mtDNA-related mitochondrial respiratory chain (MRC) complexes. One had a mutation in the EFG1 gene (GFM1; ...
Molecular genetics OMIM In an infant with combined oxidative phosphorylation deficiency, Valente et al. (2007) detected a homozygous mutation in the TUFM gene (602389.0001).