Methods Activities and amount of respiratory chain complexes were measured spectrophotometrically and by 2D-polyacrylamide gel electrophoresis. Mutations in mtDNA and genes for COX assembly proteins (SURF1, SCO1, SCO2, COX 10, COX 15) were analysed by cyclic sequencing.

Results The first clinical symptoms appeared in 78% of children in early childhood and included failure to thrive in 67% of patients, progressive encephalopathy (90%), cardiomyopathy (24%), hepatopathy (23%) and nephropathy (5%). Two-thirds of all patients died, mostly in early childhood. Blood and cerebrospinal fluid lactate was increased in 85% and 81% of examined cases, respectively. Molecular analyses established the presence of pathogenic mutations in mitochondrial or nuclear DNA in 76 patients (41%). Mutations in SURF1, SCO2 and SCO1 genes were found in 58% of children with isolated COX deficiency and mtDNA mutations or deletions were found in 30% of children with COX deficiency combined with deficiency of other respiratory chain complexes.

Conclusion COX deficiency represents a heterogeneous group of diseases with unfavourable prognosis. Detailed characterisation of COX deficiency at the molecular level is necessary for genetic counselling in affected families. Mutations 841delCT in SURF1 gene and G1541A in SCO2 gene are prevalent, at least in the Slavonic population.

Funding: Supported by MSM 0021620806 and IGA 8320-4.