Combined oxidative phosphorylation defect type 17

General Information (adopted from Orphanet):

Synonyms, Signs: COXPD17
ELAC2 mutation [IBIS]
Number of Symptoms 33
OrphanetNr: 369913
OMIM Id: 615440
ICD-10: E88.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: < 0.1 of 100 000
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

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

Comment:

Transcription of the mitochondrial genome generates large polycistronic transcripts punctuated by the 22 mitochondrial (mt) tRNAs that are conventionally cleaved by the RNase P-complex and the RNase Z activity of ELAC2 (= COXPD17) at 5' and 3' ends, respectively. ELAC2 mutations cause therefore a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy. Accumulated mtRNA precursors in affected individuals muscle and fibroblasts were observed. Although mature mt-tRNA, mt-mRNA, and mt-rRNA levels were not decreased in fibroblasts, the processing defect was associated with impaired mitochondrial translation (PMID:23849775). Involved genes: ELAC2 (COXPD17) (PMID:23849775),

Symptom Information: Sort by abundance 

1
(HPO:0002151) Increased serum lactate Frequent [IBIS] 80% (n=5) 23849775 IBIS 92 / 7739
2
(HPO:0003128) Lactic acidosis Frequent [IBIS] 60% (n=5) 23849775 IBIS 116 / 7739
3
(HPO:0001942) Metabolic acidosis Occasional [IBIS] 20% (n=5) 23849775 IBIS 81 / 7739
4
(HPO:0003218) Oroticaciduria Frequent [IBIS] 40% (n=5) 23849775 IBIS 10 / 7739
5
(HPO:0001508) Failure to thrive Occasional [IBIS] 20% (n=5) 23849775 IBIS 454 / 7739
6
(HPO:0003217) Hyperglutaminemia Frequent [IBIS] 40% (n=5) 23849775 IBIS 9 / 7739
7
(HPO:0003348) Hyperalaninemia Frequent [IBIS] 60% (n=5) 23849775 IBIS 19 / 7739
8
(HPO:0001639) Hypertrophic cardiomyopathy Very frequent [IBIS] 100% (n=5) 23849775 IBIS 137 / 7739
9
(HPO:0001644) Dilated cardiomyopathy Occasional [IBIS] 20% (n=5) 23849775 IBIS 141 / 7739
10
(HPO:0001700) Myocardial necrosis Occasional [IBIS] 20% (n=5) 23849775 IBIS 6 / 7739
11
(HPO:0001635) Congestive heart failure Frequent [IBIS] 60% (n=5) 23849775 IBIS 232 / 7739
12
(HPO:0008322) Abnormal mitochondrial morphology 23849775 IBIS 8 / 7739
13
(HPO:0003287) Abnormality of mitochondrial metabolism 23849775 IBIS 12 / 7739
14
(HPO:0008972) Decreased activity of mitochondrial respiratory chain 23849775 IBIS 34 / 7739
15
(HPO:0011923) Decreased activity of mitochondrial complex I Very frequent [IBIS] 100% (n=4) 23849775 IBIS 35 / 7739
16
(HPO:0008347) Decreased activity of mitochondrial complex IV Occasional [IBIS] 25% (n=4) 23849775 IBIS 31 / 7739
17
(HPO:0001252) Muscular hypotonia Frequent [IBIS] 60% (n=5) 23849775 IBIS 990 / 7739
18
(HPO:0008947) Infantile muscular hypotonia Frequent [IBIS] 60% (n=5) 23849775 IBIS 482 / 7739
19
(HPO:0001263) Global developmental delay Frequent [IBIS] 60% (n=5) 23849775 IBIS 853 / 7739
20
(HPO:0002015) Dysphagia Occasional [IBIS] 20% (n=5) 23849775 IBIS 301 / 7739
21
(HPO:0001511) Intrauterine growth retardation Frequent [IBIS] 40% (n=5) 23849775 IBIS 358 / 7739
22
(HPO:0000252) Microcephaly Occasional [IBIS] rare [HPO:skoehler] 20% (n=5) 23849775 IBIS 832 / 7739
23
(HPO:0000407) Sensorineural hearing impairment Occasional [IBIS] 20% (n=5) 23849775 IBIS 524 / 7739
24
(HPO:0001510) Growth delay Occasional [IBIS] 20% (n=5) 23849775 IBIS 295 / 7739
25
(HPO:0000365) Hearing impairment Occasional [IBIS] rare [HPO:skoehler] 20% (n=5) 23849775 IBIS 539 / 7739
26
(HPO:0003688) Decreased activity of cytochrome C oxidase in muscle tissue Occasional [IBIS] 20% (n=5) 23849775 IBIS 20 / 7739
27
(HPO:0002134) Abnormality of the basal ganglia Occasional [IBIS] 20% (n=5) 23849775 IBIS 13 / 7739
28
(MedDRA:10050757) Creatinine urine increased Frequent [IBIS] 40% (n=5) 23849775 IBIS 1 / 7739
29
(OMIM) Accumulation of unprocessed mt-tRNA intermediates in skeletal muscle cells and fibroblasts 23849775 IBIS 1 / 7739
30
(OMIM) COX-deficient fibers Occasional [IBIS] 20% (n=5) 23849775 IBIS 3 / 7739
31
(OMIM) Decreased mitochondrial complex IV activity (in some patients) 23849775 IBIS 1 / 7739
32
(OMIM) Heart biopsy shows enlarged mitochondrial with abnormal cristae (rare) 23849775 IBIS 1 / 7739
33
(OMIM) Hyperintensities in the basal ganglia (rare) 23849775 IBIS 1 / 7739

Associated genes:

ELAC2;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
ELAC2 rs397515463 pathogenic RCV000056274.3
ELAC2 rs397515464 pathogenic RCV000056275.2
ELAC2 rs397515465 pathogenic RCV000056276.3
ELAC2 rs397515466 pathogenic RCV000056277.3

Additional Information:

Description: (OMIM) Combined oxidative phosphorylation deficiency-17 is an autosomal recessive disorder of mitochondrial dysfunction characterized by onset of severe hypertrophic cardiomyopathy in the first year of life. Other features include hypotonia, poor growth, lactic acidosis, and failure to thrive. The ...
Clinical Description OMIM Haack et al. (2013) reported 5 patients from 3 unrelated families with onset of severe hypertrophic cardiomyopathy between 2 and 5 months of age. Two of the families were consanguineous. The infants usually presented with poor growth, hypotonia, ...
Molecular genetics OMIM In 5 patients from 3 unrelated families with combined oxidative phosphorylation deficiency-17 manifest as severe infantile-onset hypertrophic cardiomyopathy, Haack et al. (2013) identified compound heterozygous or homozygous mutations in the ELAC2 gene (605367.0006-605367.0009). The initial mutations were found ...