A NOVEL MUTATION IN THE SCO2 GENE IN A NEONATE WITH FATAL INFANTILE CARDIOENCEPHALOMYOPATHY AND COX DEFICIENCY

Objectives: To report a novel SCO2 mutation in a neonate with fatal infantile cardioencephalomyopathy and COX deficiency.

Methods: This girl was the first child of Italian healthy non-consanguineous parents. There was no family history of neurological diseases. She was referred to our NICU in 3rd day of life. On admission she presented generalized muscle hypotonia, inspiratory stridor, lactic acidosis, and severe hypertrophic cardiomyopathy (HCMP) (US study). Brain T2-MRI demonstrated generalized immature myelination still compatible with physiological pattern for the age. EMG and NCV were normal. Bronchoscopy revealed tracheomalacia. On 43rd day of life she died of cardiac failure due to progressive obstructive HCMP. Pathological groß examination confirmed the presence of obstructive HCMP of the left ventricle. Histochemical and biochemical studies of respiratory chain complexes were performed and the whole coding region of the SCO2 gene was sequenced.

Results: 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. Sequencing of the SCO2 gene showed the common E140K mutation, and a novel 2 base-pair deletion, which disrupts the reading frame of the messenger RNA and gives rise to a truncated protein.

Conclusion: We report a novel mutation in the SCO2 gene confirming the need to screen this gene in infants with severe hypotonia and hypertrophic cardiomyopathy associated with COX deficiency.