Background. Leigh disease, subacute necrotizing encephalopathy, is a serious mitochondrial disorder of energy- -providing metabolism. Clinical presentation usually starts in infancy as a progressive neurodegenerative disorder with retardation and regression of psychomotor development. The most common form of the disease is associated with deficiency of the cytochrome c oxidase (COX) due to SURF1 gene mutations. SURF1 encodes an inner mitochondrial membrane protein involved in the biogenesis and assembly of COX complex. Methods and Results. The activities of mitochondrial respiratory chain complexes were determined spectrophotometrically in isolated lymphocytes, platelets, muscle mitochondria and cultured fibroblasts. Generalised decrease of COX activity was found in 7 children with typical symptoms of Leigh disease. Two-dimensional electrophoresis of mitochondrial proteins showed altered assembly pattern of COX. As demonstrated by Western blot analysis of mitochondria or mitoplasts with anti-hSurf1 antibodies (gift fromDr. E. A. Shoubridge), the Surf1 protein was absent in all 5 investigated patients. Molecular analyses in the 7 patients revealed the presence of mutations in the SURF1 gene – six patients harboured previously described SURF1 mutations, a new mutation 574C>T was found in one patient. Conclusions. The co-operation among the patient’s families, clinicians and specialised laboratories is essential for the diagnostic of mitochondrial disorders. The treatment of Leigh syndrome is only symptomatic and the prognosis of the disease is unfavourable. The diagnostics on biochemical andmolecular level is necessary for genetic counselling and prenatal diagnosis in affected families.

        Key words: Leigh syndrome, SURF1 gene, Surf1 protein, cytochrome c oxidase.