Cytochrome c oxidase deficiency due to a novel SCO2 mutation mimics Werdnig-Hoffmann disease

Background: Mutations in the SCO2 gene have been associated with fatal cardioencephalomyopathy. Objective: To report a novel SCO2 mutation with prominent spinal cord involvement mimicking spinal muscular atrophy (Werdnig-Hoffmann disease). Patient and Methods: An infant girl presented at birth with generalized weakness, hypotonia, and lactic acidosis. At 1 month of age she developed hypertrophic cardiomyopathy and died of heart failure 1 month later. Neuroradiological studies were unremarkable. Muscle biopsy specimens showed groups of atrophic and hypertrophic fibers, but mutation screening of the SMN gene was negative. Histochemical and biochemical Studies of respiratory chain complexes were performed, and the whole coding region of the SCO2 gene was sequenced. Results: Findings from muscle histochemistry studies showed virtually undetectable cytochrome c oxidase activity, but normal succinate dehydrogenase reaction. Biochemical analysis in muscle confirmed a severe isolated cytochrome c oxidase deficiency. Pathologic findings of the brain were unremarkable, but the ventral horns of the spinal cord showed moderate-to-severe loss of motor neurons and astrocytosis. Sequencing of the SCO2 gene showed the common E140K mutation, and a novel 10 base-pair duplication of nucleotides 1302 to 1311, which disrupts the reading frame of the messenger RNA and gives rise to a truncated protein. Conclusion: The SCO2 mutations should be considered in the differential diagnosis of children with spinal muscular atrophy without mutations in the SMN gene.