Hepatoencephalopathy due to combined oxidative phosphorylation deficiency type 1

General Information (adopted from Orphanet):

Synonyms, Signs: COXPD1
Hepatoencephalopathy due to COXPD1
Hepatoencephalopathy, early fatal progressive
Number of Symptoms 69
OrphanetNr: 137681
OMIM Id: 609060
ICD-10: E88.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Monogenic
Autosomal recessive
26937387 [IBIS]
Age of onset: Neonatal
26937387 [IBIS]

Disease classification (adopted from Orphanet):

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

Comment:

GFM1 (= COXPD1, EFG1) is a GTPase, which catalyzes the translocation step of mitochondrial protein synthesis. The process involves the movement of peptidyl-tRNA from the ribosomal-acceptor (A) site to the peptidyl (P) site following removal of a deacylated tRNA from the peptidyl (P) site to the ribosomal exit (E) site. This movement results in advancement of the mRNA by one codon and subsequently leaves the ribosomal-acceptor (A) site available for a new elongation cycle. The biochemical deficiency in patients with GFM1 mutations is a combined OXPHOS deficiency, without any quantitative or qualitative mtDNA abnormalities (PMID:26937387).

Symptom Information: Sort by abundance 

1
 (HPO:0011968) Feeding difficulties Very frequent [IBIS] 26937387 IBIS 240 / 7739
2
 (HPO:0002013) Vomiting Rare [IBIS] 7% (n=14) 26937387 IBIS 191 / 7739
3
 (HPO:0007738) Uncontrolled eye movements Rare [IBIS] 7% (n=14) 26937387 IBIS 3 / 7739
4
 (HPO:0000639) Nystagmus Occasional [IBIS] 14% (n=14) 26937387 IBIS 555 / 7739
5
 (HPO:0000486) Strabismus Rare [IBIS] 7% (n=14) 26937387 IBIS 576 / 7739
6
 (HPO:0000508) Ptosis Rare [IBIS] 7% (n=14) 26937387 IBIS 459 / 7739
7
 (HPO:0002151) Increased serum lactate Frequent [IBIS] 64% (n=14) 26937387 IBIS 92 / 7739
8
 (HPO:0003128) Lactic acidosis Frequent [IBIS] 36% (n=14) 26937387 IBIS 116 / 7739
9
 (HPO:0001942) Metabolic acidosis Very frequent [IBIS] 26937387 IBIS 81 / 7739
10
 (HPO:0001508) Failure to thrive Rare [IBIS] 7% (n=14) 26937387 IBIS 454 / 7739
11
 (HPO:0001998) Neonatal hypoglycemia Occasional [IBIS] 21% (n=14) 26937387 IBIS 22 / 7739
12
 (HPO:0002119) Ventriculomegaly Rare [IBIS] 7% (n=14) 26937387 IBIS 253 / 7739
13
 (HPO:0011925) Decreased activity of mitochondrial ATP synthase complex 26937387 IBIS 10 / 7739
14
 (HPO:0011923) Decreased activity of mitochondrial complex I 26937387 IBIS 35 / 7739
15
 (HPO:0011924) Decreased activity of mitochondrial complex III 26937387 IBIS 22 / 7739
16
 (HPO:0008347) Decreased activity of mitochondrial complex IV 26937387 IBIS 31 / 7739
17
 (HPO:0003073) Hypoalbuminemia Rare [IBIS] 7% (n=14) 26937387 IBIS 40 / 7739
18
 (HPO:0003256) Abnormality of the coagulation cascade Rare [IBIS] 7% (n=14) 26937387 IBIS 19 / 7739
19
 (HPO:0002058) Myopathic facies Rare [IBIS] 7% (n=14) 26937387 IBIS 26 / 7739
20
 (HPO:0001397) Hepatic steatosis Rare [IBIS] 7% (n=14) 26937387 IBIS 75 / 7739
21
 (HPO:0001252) Muscular hypotonia Frequent [IBIS] 26937387 IBIS 990 / 7739
22
 (HPO:0002490) Increased CSF lactate Occasional [IBIS] 14% (n=14) 26937387 IBIS 28 / 7739
23
 (HPO:0001271) Polyneuropathy Rare [IBIS] 7% (n=14) 26937387 IBIS 56 / 7739
24
 (HPO:0001347) Hyperreflexia Rare [IBIS] 7% (n=14) 26937387 IBIS 363 / 7739
25
 (HPO:0001276) Hypertonia Frequent [IBIS] 26937387 IBIS 317 / 7739
26
 (HPO:0001257) Spasticity Occasional [IBIS] 14% (n=14) 26937387 IBIS 251 / 7739
27
 (HPO:0002179) Opisthotonus Rare [IBIS] 7% (n=14) 26937387 IBIS 35 / 7739
28
 (HPO:0001332) Dystonia Occasional [IBIS] 14% (n=14) 26937387 IBIS 197 / 7739
29
 (HPO:0000817) Poor eye contact Occasional [IBIS] 14% (n=14) 26937387 IBIS 26 / 7739
30
 (HPO:0001263) Global developmental delay Very frequent [IBIS] 26937387 IBIS 853 / 7739
31
 (HPO:0004372) Reduced consciousness/confusion Rare [IBIS] 7% (n=14) 26937387 IBIS 73 / 7739
32
 (HPO:0002375) Hypokinesia Rare [IBIS] 7% (n=14) 26937387 IBIS 25 / 7739
33
 (HPO:0002521) Hypsarrhythmia Rare [IBIS] 7% (n=14) 26937387 IBIS 43 / 7739
34
 (HPO:0001250) Seizures Occasional [IBIS] 21% (n=14) 26937387 IBIS 1245 / 7739
35
 (HPO:0001511) Intrauterine growth retardation Occasional [IBIS] 29% (n=14) 26937387 IBIS 358 / 7739
36
 (HPO:0001562) Oligohydramnios Rare [IBIS] 7% (n=14) 26937387 IBIS 75 / 7739
37
 (HPO:0000252) Microcephaly Frequent [IBIS] 50% (n=14) 26937387 IBIS 832 / 7739
38
 (HPO:0002079) Hypoplasia of the corpus callosum Occasional [IBIS] 21% (n=14) 26937387 IBIS 161 / 7739
39
 (HPO:0001408) Bile duct proliferation Rare [IBIS] 7% (n=14) 26937387 IBIS 22 / 7739
40
 (HPO:0001396) Cholestasis Occasional [IBIS] 14% (n=14) 26937387 IBIS 136 / 7739
41
 (HPO:0001394) Cirrhosis Rare [IBIS] 7% (n=14) 26937387 IBIS 102 / 7739
42
 (HPO:0001410) Decreased liver function Occasional [IBIS] 14% (n=14) 26937387 IBIS 59 / 7739
43
 (HPO:0001399) Hepatic failure Frequent [IBIS] 79% (n=14) 26937387 IBIS 80 / 7739
44
 (HPO:0002240) Hepatomegaly Occasional [IBIS] 14% (n=14) 26937387 IBIS 467 / 7739
45
 (HPO:0001541) Ascites Rare [IBIS] 7% (n=14) 26937387 IBIS 94 / 7739
46
 (HPO:0000047) Hypospadias Rare [IBIS] 7% (n=14) 26937387 IBIS 250 / 7739
47
 (HPO:0000807) Glandular hypospadias Rare [IBIS] 7% (n=14) 26937387 IBIS 3 / 7739
48
 (HPO:0001999) Abnormal facial shape Rare [IBIS] 7% (n=14) 26937387 IBIS 169 / 7739
49
 (HPO:0000280) Coarse facial features Rare [IBIS] 7% (n=14) 26937387 IBIS 189 / 7739
50
 (HPO:0000799) Renal steatosis Rare [IBIS] 7% (n=14) 26937387 IBIS 6 / 7739
51
 (HPO:0002904) Hyperbilirubinemia Rare [IBIS] 7% (n=14) 26937387 IBIS 32 / 7739
52
 (HPO:0007371) Corpus callosum atrophy 26937387 IBIS 14 / 7739
53
 (HPO:0006799) Basal ganglia cysts Rare [IBIS] 7% (n=14) 26937387 IBIS 6 / 7739
54
 (HPO:0001320) Cerebellar vermis hypoplasia Rare [IBIS] 7% (n=14) 26937387 IBIS 57 / 7739
55
 (HPO:0002059) Cerebral atrophy Rare [IBIS] 7% (n=14) 26937387 IBIS 171 / 7739
56
 (HPO:0012448) Delayed myelination Rare [IBIS] 7% (n=14) 26937387 IBIS 51 / 7739
57
 (HPO:0002283) Global brain atrophy 26937387 IBIS 12 / 7739
58
 (HPO:0002415) Leukodystrophy Rare [IBIS] 7% (n=14) 26937387 IBIS 30 / 7739
59
 (HPO:0002126) Polymicrogyria Occasional [IBIS] 14% (n=14) 26937387 IBIS 64 / 7739
60
 (HPO:0002132) Porencephaly Rare [IBIS] 7% (n=14) 26937387 IBIS 18 / 7739
61
 (HPO:0002878) Respiratory failure Rare [IBIS] 7% (n=14) 26937387 IBIS 57 / 7739
62
 (OMIM) 'Stiffness' 26937387 IBIS 5 / 7739
63
 (OMIM) Agenesis of the cingulate gyrus 26937387 IBIS 2 / 7739
64
 (OMIM) Borderline microcephaly 26937387 IBIS 3 / 7739
65
 (OMIM) Increased iron deposition seen on liver biopsy 26937387 IBIS 2 / 7739
66
 (OMIM) Increased serum direct bilirubin 26937387 IBIS 1 / 7739
67
 (OMIM) Liver necrosis 26937387 IBIS 2 / 7739
68
 (OMIM) Metabolic acidosis, severe 26937387 IBIS 2 / 7739
69
 (OMIM) Wandering eye movements 26937387 IBIS 2 / 7739

Associated genes:

GFM1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Combined oxidative phosphorylation deficiency is an autosomal recessive multisystem disorder with variable manifestations resulting from a defect in the mitochondrial oxidative phosphorylation (OXPHOS) system. Onset occurs at or soon after birth, and features can include growth retardation, microcephaly, ...
Clinical Description OMIM Coenen et al. (2004) described 2 sibs, born of consanguineous Lebanese parents, who died at ages 27 days and 5 months, respectively, and were found to have a severe defect in mitochondrial translation, reduced levels of oxidative phosphorylation ...
Molecular genetics OMIM By sequence analysis of the EFG1 gene, which had been mapped within the critical region for combined oxidative phosphorylation deficiency, Coenen et al. (2004) identified a homozygous asn174-to-ser mutation in the EFG1 gene (N174S; 606639.0001) in affected sibs. ...