A homozygous mutation in the SCO2 gene causes a spinal muscular atrophy like presentation with stridor and respiratory insufficiency

Infants with deficiency of cytochrome c oxidase (COX) due to SCO2 mutations observed so far usually demonstrated early cardiomyopathy, encephalopathy and lactic acidosis. Milder spinal muscular atrophy-like (SMA-like) phenotype was also rarely reported.The aim is to present 18 Polish patients with SCO2 mutations. Molecular study revealed p.E140K mutation in all cases (on 32 alleles); p.Q53X mutation and novel p.M177T change were identified in single patients. In three families no second mutation was found.Thirteen p.E140K homozygotes presented in infancy with floppiness and remarkable stridor. Survival motor neuron (SMN) gene deletion was excluded. Mild to moderate lactic academia was found. Neurological involvement manifested as spasticity and psychomotor retardation. In some patients strabismus, ptosis and episodes of seizures were seen. During second half of the year chronic respiratory failure with artificial respiration dependency appeared in all homozygotes. Heart involvement was never present at the beginning. Rapidly progressive hypertrophic cardiomyopathy developed in several patients at the terminal stage. The stridor was constant and striking feature.Skeletal muscle biopsy was performed in 16 patients including 11 homozygotes. Four pathological patterns were discerned – from neurogenic muscle changes, including spinal muscular atrophy (SMA) to unspecific findings. Histochemical cytochrome c oxidase (COX) deficit was not a constant feature. Significant decrease in respiratory chain complex IV activity was detected in muscle homogenate by spectrophotometric method only in 7 out of 12 examined cases.Conclusions1/Mutations of SCO2 gene should be considered as a possible cause of neurogenic skeletal muscle features (including SMA-like) in infants with encephalomyopathy even in the absence of heart involvement and COX deficit; 2/Inspiratory stridor may be symptomatic of SCO2 gene mutation(s).