Combined oxidative phosphorylation defect type 8

General Information (adopted from Orphanet):

Synonyms, Signs: COXPD8
Cardiomyopathy, hypertrophic mitochondrial, fatal infantile
Number of Symptoms 42
OrphanetNr: 319504
OMIM Id: 614096
ICD-10: I42.2
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Monogenic
Autosomal recessive
21549344 [IBIS]
Age of onset: Neonatal
Infancy
Childhood
Adolescent
21549344 [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:

Age at onset: 1 day–15 yrs (PMID:21549344). AARS2 (= COXPD8) mutations cause a near-total deficiency of respiratory chain (RC) complexes in the heart of the patients, leading to primary manifestation as a primary mitochondrial cardiomyopathy (CMP), and cause partial deficiency of RC complexes in the skeletal muscle and brain but not in the liver. The severe CMP led to early death of the patients, but the reduction of RC complexes in the other tissues indicated multiorgan manifestation (PMID:21549344).

Symptom Information: Sort by abundance 

1
 (HPO:0011968) Feeding difficulties 21549344 IBIS 240 / 7739
2
 (HPO:0008872) Feeding difficulties in infancy 21549344 IBIS 153 / 7739
3
 (HPO:0002089) Pulmonary hypoplasia 21549344 IBIS 80 / 7739
4
 (HPO:0003128) Lactic acidosis 21549344 IBIS 116 / 7739
5
 (HPO:0001942) Metabolic acidosis 21549344 IBIS 81 / 7739
6
 (HPO:0001508) Failure to thrive 21549344 IBIS 454 / 7739
7
 (HPO:0003219) Ethylmalonic aciduria 21549344 IBIS 5 / 7739
8
 (HPO:0001640) Cardiomegaly 21549344 IBIS 81 / 7739
9
 (HPO:0001712) Left ventricular hypertrophy 21549344 IBIS 76 / 7739
10
 (HPO:0006693) Myocardial steatosis 21549344 IBIS 2 / 7739
11
 (HPO:0001639) Hypertrophic cardiomyopathy Very frequent [IBIS] 21549344 IBIS 137 / 7739
12
 (HPO:0001644) Dilated cardiomyopathy 21549344 IBIS 141 / 7739
13
 (HPO:0001635) Congestive heart failure 21549344 IBIS 232 / 7739
14
 (HPO:0006670) Impaired myocardial contractility 21549344 IBIS 9 / 7739
15
 (HPO:0008972) Decreased activity of mitochondrial respiratory chain Very frequent [IBIS] 21549344 IBIS 34 / 7739
16
 (HPO:0011923) Decreased activity of mitochondrial complex I 21549344 IBIS 35 / 7739
17
 (HPO:0011924) Decreased activity of mitochondrial complex III 21549344 IBIS 22 / 7739
18
 (HPO:0008347) Decreased activity of mitochondrial complex IV 21549344 IBIS 31 / 7739
19
 (HPO:0001397) Hepatic steatosis 21549344 IBIS 75 / 7739
20
 (HPO:0009058) Increased muscle lipid content 21549344 IBIS 6 / 7739
21
 (HPO:0011807) Type 1 muscle fiber atrophy 21549344 IBIS 2 / 7739
22
 (HPO:0003324) Generalized muscle weakness 21549344 IBIS 48 / 7739
23
 (HPO:0001270) Motor delay 21549344 IBIS 322 / 7739
24
 (HPO:0002353) EEG abnormality 21549344 IBIS 188 / 7739
25
 (HPO:0001315) Reduced tendon reflexes 21549344 IBIS 160 / 7739
26
 (HPO:0003800) Muscle abnormality related to mitochondrial dysfunction 21549344 IBIS 3 / 7739
27
 (HPO:0003688) Decreased activity of cytochrome C oxidase in muscle tissue 21549344 IBIS 20 / 7739
28
 (HPO:0001522) Death in infancy 21549344 IBIS 275 / 7739
29
 (HPO:0003811) Neonatal death 21549344 IBIS 44 / 7739
30
 (HPO:0003676) Progressive disorder 21549344 IBIS 148 / 7739
31
 (HPO:0003826) Stillbirth 21549344 IBIS 40 / 7739
32
 (MedDRA:10033318) Oxygen saturation decreased 21549344 IBIS 4 / 7739
33
 (OMIM) COX deficiency 21549344 IBIS 2 / 7739
34
 (OMIM) Cardiomyopathy, mitochondrial 21549344 IBIS 2 / 7739
35
 (OMIM) Decreased contractility 21549344 IBIS 2 / 7739
36
 (OMIM) Decreased mitochondrial respiratory complexes I, III, and IV in brain, heart, and skeletal muscle 21549344 IBIS 1 / 7739
37
 (OMIM) Fiber size variation 21549344 IBIS 3 / 7739
38
 (OMIM) Infantile cardiomyopathy 21549344 IBIS 3 / 7739
39
 (OMIM) Periodic stiffness 21549344 IBIS 1 / 7739
40
 (OMIM) Pulmonary hypoplasia, mild 21549344 IBIS 1 / 7739
41
 (OMIM) Staring gaze 21549344 IBIS 2 / 7739
42
 (OMIM) Vacuolization 21549344 IBIS 2 / 7739

Associated genes:

AARS2;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) COXPD8 is an autosomal recessive disorder due to dysfunction of the mitochondrial respiratory chain. The main clinical manifestation is a lethal infantile hypertrophic cardiomyopathy, but there is also subtle skeletal muscle and brain involvement. Biochemical studies show combined ...
Clinical Description OMIM Gotz et al. (2011) reported a Finnish girl who presented at age 3.5 months with failure to thrive, delayed motor development, and severe generalized muscle weakness. She was found to have severe hypertrophic cardiomyopathy with decreased contractility and ...
Molecular genetics OMIM By exome sequencing, Gotz et al. (2011) identified a homozygous mutation in the AARS2 gene (R592W; 612035.0001) in a Finnish girl with fatal infantile hypertrophic mitochondrial cardiomyopathy. A second Finnish female infant with a more severe mitochondrial cardiomyopathy ...