Combined oxidative phosphorylation defect type 15

General Information (adopted from Orphanet):

Synonyms, Signs: COXPD15
Number of Symptoms 68
OrphanetNr: 319524
OMIM Id: 614947
ICD-10: G31.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Monogenic
Autosomal recessive
23499752 [IBIS]
Age of onset: Infancy
Childhood
Adolescent
24461907 [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:

Mutations in mitochondrial methionyl-tRNA formyltransferase (MTFMT = COXPD15) underlie a human disorder of formylation causing impaired mitochondrial translation (PMID:21907147).

Symptom Information: Sort by abundance 

1
 (HPO:0000648) Optic atrophy Occasional [IBIS] rare [HPO:skoehler] 13% (n=16) 24461907 IBIS 238 / 7739
2
 (HPO:0000543) Optic disc pallor Rare [IBIS] 6% (n=16) 24461907 IBIS 67 / 7739
3
 (HPO:0000639) Nystagmus rare [HPO:skoehler] 24461907 IBIS 555 / 7739
4
 (HPO:0000602) Ophthalmoplegia Occasional [IBIS] 13% (n=16) 24461907 IBIS 56 / 7739
5
 (HPO:0000486) Strabismus Occasional [IBIS] rare [HPO:skoehler] 19% (n=16) 24461907 IBIS 576 / 7739
6
 (HPO:0000505) Visual impairment Rare [IBIS] rare [HPO:skoehler] 6% (n=16) 24461907 IBIS 297 / 7739
7
 (HPO:0007663) Reduced visual acuity rare [HPO:skoehler] 24461907 IBIS 100 / 7739
8
 (HPO:0002090) Pneumonia Rare [IBIS] 6% (n=16) 24461907 IBIS 59 / 7739
9
 (HPO:0002151) Increased serum lactate rare [HPO:skoehler] 24461907 IBIS 92 / 7739
10
 (HPO:0003128) Lactic acidosis Frequent [IBIS] 38% (n=16) 24461907 IBIS 116 / 7739
11
 (HPO:0004900) Severe lactic acidosis Rare [IBIS] 6% (n=16) 24461907 IBIS 5 / 7739
12
 (HPO:0004322) Short stature Occasional [IBIS] rare [HPO:skoehler] 13% (n=16) 24461907 IBIS 1232 / 7739
13
 (HPO:0003542) Increased serum pyruvate Rare [IBIS] 6% (n=16) 24461907 IBIS 18 / 7739
14
 (HPO:0001629) Ventricular septal defect Rare [IBIS] rare [HPO:skoehler] 6% (n=16) 24461907 IBIS 316 / 7739
15
 (HPO:0001638) Cardiomyopathy Occasional [IBIS] 13% (n=16) 24461907 IBIS 192 / 7739
16
 (HPO:0001639) Hypertrophic cardiomyopathy Rare [IBIS] 6% (n=16) 24461907 IBIS 137 / 7739
17
 (HPO:0001716) Wolff-Parkinson-White syndrome Occasional [IBIS] rare [HPO:skoehler] 13% (n=16) 24461907 IBIS 21 / 7739
18
 (HPO:0012102) Abnormal mitochondrial number Rare [IBIS] 6% (n=16) 24461907 IBIS 4 / 7739
19
 (HPO:0011925) Decreased activity of mitochondrial ATP synthase complex 23499752 IBIS 10 / 7739
20
 (HPO:0011923) Decreased activity of mitochondrial complex I 23499752 IBIS 35 / 7739
21
 (HPO:0008347) Decreased activity of mitochondrial complex IV 23499752 IBIS 31 / 7739
22
 (HPO:0000824) Growth hormone deficiency Rare [IBIS] 6% (n=16) 24461907 IBIS 56 / 7739
23
 (HPO:0009058) Increased muscle lipid content Rare [IBIS] 6% (n=16) 24461907 IBIS 6 / 7739
24
 (HPO:0001252) Muscular hypotonia Frequent [IBIS] rare [HPO:skoehler] 50% (n=16) 24461907 IBIS 990 / 7739
25
 (HPO:0008947) Infantile muscular hypotonia 24461907 IBIS 482 / 7739
26
 (HPO:0001324) Muscle weakness 24461907 IBIS 859 / 7739
27
 (HPO:0002490) Increased CSF lactate Occasional [IBIS] 31% (n=16) 24461907 IBIS 28 / 7739
28
 (HPO:0001251) Ataxia Occasional [IBIS] rare [HPO:skoehler] 19% (n=16) 24461907 IBIS 413 / 7739
29
 (HPO:0002066) Gait ataxia Occasional [IBIS] 13% (n=16) 24461907 IBIS 327 / 7739
30
 (HPO:0002311) Incoordination 23499752 IBIS 84 / 7739
31
 (HPO:0007256) Abnormal pyramidal signs Rare [IBIS] 6% (n=16) 24461907 IBIS 116 / 7739
32
 (HPO:0002061) Lower limb spasticity Rare [IBIS] 6% (n=16) 24461907 IBIS 56 / 7739
33
 (HPO:0006986) Upper limb spasticity Rare [IBIS] 6% (n=16) 24461907 IBIS 15 / 7739
34
 (HPO:0012434) Delayed social development 24461907 IBIS 1 / 7739
35
 (HPO:0010522) Dyslexia 23499752 IBIS 7 / 7739
36
 (HPO:0001260) Dysarthria Rare [IBIS] 6% (n=16) 24461907 IBIS 329 / 7739
37
 (HPO:0001263) Global developmental delay Frequent [IBIS] 69% (n=16) 24461907 IBIS 853 / 7739
38
 (HPO:0011342) Mild global developmental delay 24461907 IBIS 10 / 7739
39
 (HPO:0011344) Severe global developmental delay 24461907 IBIS 46 / 7739
40
 (HPO:0001249) Intellectual disability Occasional [IBIS] 13% (n=16) 24461907 IBIS 1089 / 7739
41
 (HPO:0010862) Delayed fine motor development Rare [IBIS] 6% (n=16) 24461907 IBIS 3 / 7739
42
 (HPO:0002194) Delayed gross motor development Rare [IBIS] 6% (n=16) 24461907 IBIS 37 / 7739
43
 (HPO:0012431) Episodic fatigue Rare [IBIS] 6% (n=16) 24461907 IBIS 1 / 7739
44
 (HPO:0100543) Cognitive impairment Rare [IBIS] 6% (n=16) 24461907 IBIS 230 / 7739
45
 (HPO:0000750) Delayed speech and language development Rare [IBIS] 6% (n=16) 24461907 IBIS 197 / 7739
46
 (HPO:0002317) Unsteady gait Rare [IBIS] 6% (n=16) 24461907 IBIS 45 / 7739
47
 (HPO:0001337) Tremor Rare [IBIS] rare [HPO:skoehler] 6% (n=16) 24461907 IBIS 200 / 7739
48
 (HPO:0001250) Seizures rare [HPO:skoehler] 24461907 IBIS 1245 / 7739
49
 (HPO:0002069) Generalized tonic-clonic seizures 24461907 IBIS 96 / 7739
50
 (HPO:0000252) Microcephaly Frequent [IBIS] rare [HPO:skoehler] 38% (n=16) 24461907 IBIS 832 / 7739
51
 (HPO:0001578) Hypercortisolism Rare [IBIS] 6% (n=16) 24461907 IBIS 17 / 7739
52
 (HPO:0002893) Pituitary adenoma Rare [IBIS] 6% (n=16) 24461907 IBIS 16 / 7739
53
 (HPO:0005957) Breathing dysregulation 24461907 IBIS 6 / 7739
54
 (HPO:0001510) Growth delay 24461907 IBIS 295 / 7739
55
 (HPO:0002500) Abnormality of the cerebral white matter 24461907 IBIS 73 / 7739
56
 (HPO:0011441) Abnormality of the medulla oblongata Occasional [IBIS] 18% (n=11) 24461907 IBIS 4 / 7739
57
 (HPO:0002120) Cerebral cortical atrophy 24461907 IBIS 187 / 7739
58
 (HPO:0012748) Focal T2 hyperintense brainstem lesion 24461907 IBIS 2 / 7739
59
 (HPO:0007183) Focal T2 hyperintense basal ganglia lesion 24461907 IBIS 6 / 7739
60
 (HPO:0002878) Respiratory failure Rare [IBIS] 6% (n=16) 24461907 IBIS 57 / 7739
61
 (HPO:0007039) Symmetric lesions of the basal ganglia Frequent [IBIS] 64% (n=11) 24461907 IBIS 2 / 7739
62
 (IBIS) Leigh-like lesions on brain magnetic resonance imaging (MRI) 24461907 IBIS 3 / 7739
63
 (MedDRA:10069632) Bladder dysfunction 24461907 IBIS 3 / 7739
64
 (OMIM) Abnormal breathing pattern 24461907 IBIS 8 / 7739
65
 (OMIM) Difficulty reading 23499752 IBIS 2 / 7739
66
 (OMIM) Impaired mitochondrial translation 24461907 IBIS 4 / 7739
67
 (OMIM) Leigh syndrome 24461907 IBIS 7 / 7739
68
 (OMIM) Subsarcolemmal mitochondrial accumulation 24461907 IBIS 4 / 7739

Associated genes:

MTFMT;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Tucker et al. (2011) reported 2 unrelated probands with combined oxidative phosphorylation deficiency. The first patient presented at age 9 years with acquired strabismus and mildly decreased visual acuity. She had a history of mild developmental delay affecting ...
Molecular genetics OMIM In 2 unrelated patients with COXPD15, Tucker et al. (2011) identified compound heterozygosity for 2 mutations in the MTFMT gene (611766.0001-611766.0003). The mutations were identified by next-generation sequencing of coding exons from nuclear-encoded mitochondrial-associated genes. MTFMT activity was ...