Cardioencephalomyopathy, Fatal Infantile, Due To Cytochrome C Oxidase Deficiency 3

A number sign (#) is used with this entry because of evidence that fatal infantile cardioencephalomyopathy due to cytochrome c oxidase (COX) deficiency-3 (CEMCOX3) is caused by homozygous mutation in the COA5 gene (613920) on chromosome 2q11. One such family has been reported.

For a general phenotypic description and a discussion of genetic heterogeneity of fatal infantile cardioencephalomyopathy due to cytochrome c oxidase deficiency, see CEMCOX1 (604377).

Clinical Features

Huigsloot et al. (2011) reported 2 sibs, born of consanguineous Turkish parents, with cytochrome c oxidase deficiency manifest as lethal neonatal hypertrophic cardiomyopathy. The patients died at ages 8 and 10 days. Postmortem examination showed accumulation of lipid droplets in cardiomyocytes and mitochondrial proliferation; however, neither patient had documented functional impairment of brain or skeletal muscle.

Inheritance

The transmission pattern of CEMCOX3 in the family reported by Huigsloot et al. (2011) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 2 sibs, born of consanguineous Turkish parents, with CEMCOX3, Huigsloot et al. (2011) identified a homozygous mutation in the C2ORF64 (COA5) gene (A53P; 613920.0001). The activity and amount of complex IV were severely reduced in patient fibroblasts and heart muscle, and the complex IV subcomplexes lacked mitochondrial subunits COX1 (516030), COX2 (516040), COX4 (123864), and COX5A (603773). Complementation of patient fibroblasts with wildtype C2ORF64 resulted in normalization of fully assembled complex IV.