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
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.
Leigh syndrome, SURF1 gene, Surf1 protein, cytochrome c oxidase.