Combined oxidative phosphorylation defect type 11

General Information (adopted from Orphanet):

Synonyms, Signs: COXPD11
Encephaloneuromyopathy, infantile, due to mitochondrial translation defect
Number of Symptoms 35
OrphanetNr: 324535
OMIM Id: 614922
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: < 0.1 of 100 000
Inheritance: Monogenic
Autosomal recessive
23022099 [IBIS]
Age of onset: Neonatal
Infancy
23022099 [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
Neurometabolic disease
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Ferreiro-Barros et al. (2008) describe a child who presented with severe congenital encephalopathy, peripheral neuropathy, myopathy, and lactic acidosis associated with deficiencies of multiple mitochondrial respiratory-chain enzymes and defective mitochondrial translation. In Garcia-Diaz et al. (2012) four additional affected family members have been characterized. Homozygosity mapping was performed, and a homozygous splicing mutation in the splice donor site of exon 2 (c.504+1G>A) of RMND1 (required for meiotic nuclear division-1) in the affected individuals identified. RMND1 (= COXPD11, C6orf96, RMD1) belongs to the sif2 family, an evolutionary conserved group of proteins that share the DUF155 domain (PMID:23022099).

Symptom Information: Sort by abundance 

1
 (HPO:0002151) Increased serum lactate 18835491 IBIS 92 / 7739
2
 (HPO:0003128) Lactic acidosis 23022099 IBIS 116 / 7739
3
 (HPO:0008972) Decreased activity of mitochondrial respiratory chain 23022099 IBIS 34 / 7739
4
 (HPO:0011925) Decreased activity of mitochondrial ATP synthase complex 23022099 IBIS 10 / 7739
5
 (HPO:0011923) Decreased activity of mitochondrial complex I 23022099 IBIS 35 / 7739
6
 (HPO:0011924) Decreased activity of mitochondrial complex III 26238252 IBIS 22 / 7739
7
 (HPO:0008347) Decreased activity of mitochondrial complex IV 23022099 IBIS 31 / 7739
8
 (HPO:0003198) Myopathy 23022099 IBIS 151 / 7739
9
 (HPO:0001252) Muscular hypotonia 23022099 IBIS 990 / 7739
10
 (HPO:0008947) Infantile muscular hypotonia 23022099 IBIS 482 / 7739
11
 (HPO:0006829) Severe muscular hypotonia 23022099 IBIS 29 / 7739
12
 (HPO:0001308) Tongue fasciculations rare [HPO:skoehler] 23022099 IBIS 18 / 7739
13
 (HPO:0001336) Myoclonus rare [HPO:skoehler] 23022099 IBIS 115 / 7739
14
 (HPO:0002490) Increased CSF lactate 18835491 IBIS 28 / 7739
15
 (HPO:0002922) Increased CSF protein 18835491 IBIS 27 / 7739
16
 (HPO:0007239) Congenital encephalopathy 23022099 IBIS 2 / 7739
17
 (HPO:0009830) Peripheral neuropathy rare [HPO:skoehler] 23022099 IBIS 206 / 7739
18
 (HPO:0001254) Lethargy 23022099 IBIS 104 / 7739
19
 (HPO:0002353) EEG abnormality 18835491 IBIS 188 / 7739
20
 (HPO:0001284) Areflexia 23022099 IBIS 198 / 7739
21
 (HPO:0001265) Hyporeflexia 23022099 IBIS 208 / 7739
22
 (HPO:0001760) Abnormality of the foot 18835491 IBIS 96 / 7739
23
 (HPO:0001072) Thickened skin 26238252 IBIS 87 / 7739
24
 (HPO:0006808) Cerebral hypomyelination 18835491 IBIS 16 / 7739
25
 (HPO:0003819) Death in childhood 23022099 IBIS 42 / 7739
26
 (HPO:0001522) Death in infancy 23022099 IBIS 275 / 7739
27
 (HPO:0003429) CNS hypomyelination 18835491 IBIS 21 / 7739
28
 (HPO:0001302) Pachygyria 18835491 IBIS 60 / 7739
29
 (HPO:0002878) Respiratory failure 23022099 IBIS 57 / 7739
30
 (OMIM) Equinus foot deformities 18835491 IBIS 1 / 7739
31
 (OMIM) Floppiness 23022099 IBIS 1 / 7739
32
 (OMIM) Little spontaneous limb movement 23022099 IBIS 1 / 7739
33
 (OMIM) Prominent sulci 18835491 IBIS 1 / 7739
34
 (OMIM) Respiratory insufficiency requiring mechanical ventilation (1 family) 23022099 IBIS 1 / 7739
35
 (OMIM) Sural nerve biopsy shows lack of myelinated fibers (1 patient) 18835491 IBIS 1 / 7739

Associated genes:

RMND1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) COXPD11 is a severe multisystemic autosomal recessive disorder characterized by neonatal hypotonia and lactic acidosis. Affected individuals may have respiratory insufficiency, foot deformities, or seizures, and all reported patients have died in infancy. Biochemical studies show deficiencies of ...
Clinical Description OMIM Ferreiro-Barros et al. (2008) reported a male infant, born of consanguineous Saudi Arabian parents, with severe neonatal encephalopathy resulting in death at age 18 months. The infant was unresponsive at birth, but was successfully resuscitated and intubated. He ...
Molecular genetics OMIM By homozygosity mapping followed by candidate gene sequencing of a family with COXPD11, Garcia-Diaz et al. (2012) identified a homozygous pathogenic mutation in the RMND1 gene (614917.0001) that segregated with the disorder. Unaffected parents were heterozygous for the ...