Clinical, biochemical and molecular analyses of six patients with isolated cytochrome c oxidase deficiency due to mutations in the SCO2 gene.

BACKGROUND AND AIM: Cytochrome c oxidase (COX) deficiency represents a heterogeneous group of disorders. Numerous proteins are required for efficient COX assembly and maintenance. In 26 children with isolated COX deficiency, we studied mutations in the SCO2 gene, which is involved in the copper transport into the inner mitochondrial membrane, and we analysed the clinical and biochemical consequences of SCO2 mutations.
METHODS: The activities of respiratory chain complexes were measured spectrophotometrically in isolated mitochondria and/or crude cell extracts in all available tissues. Two-dimensional polyacrylamide electrophoresis (2D-PAGE) was used to separate the complexes and their subunits. The mutations were detected by sequencing and RFLP analysis.
RESULTS: Mutations in the SCO2 gene were found in six children. Early neonatal onset of hypertrophic cardiomyopathy and encephalopathy were observed in one boy with compound heterozygous mutations C1280T and G1541A. In all five children with homozygous mutation G1541A, progressive encephalopathy developed between 2 and 6 mo of age. Isolated COX deficiency was found in the skeletal muscle, heart, liver and brain but not in fibroblasts. 2D-PAGE in the skeletal muscle showed markedly decreased amounts of all COX subunits.
CONCLUSION: Our results suggest that mutations in the SCO2 gene are not rare, at least in our population. Although clinical symptoms may rely on the type of SCO2 mutation, the prognosis is unfavourable in all patients.