Novel LRPPRC Mutation in a Boy With Mild Leigh Syndrome, French–Canadian Type Outside of Québec

BACKGROUND: Leigh syndrome, French–Canadian type is unique to patients from a genetic isolate in the Saguenay–Lac-Saint-Jean region of Québec. It has also been recently described in 10 patients with LRPPRC mutation outside of Québec. It is an autosomal recessive genetic disorder with fatal metabolic crisis and severe neurological morbidity in infancy caused by LRPPRC mutation. METHODS AND RESULTS: The authors report a boy with a novel LRPPRC compound heterozygous missense mutations c.3130C>T, c.3430C>T, and c.4078G>A found on whole-exome sequencing which correlated with isolated cytochrome c-oxidase deficiency found in skeletal muscle. CONCLUSION: LRPPRC mutation is a rare cause of cytochrome c-oxidase–deficient form of Leigh syndrome outside of Québec. Our patient broadens the spectrum of phenotypes of Leigh syndrome, French–Canadian type. LRPPRC mutation should be considered in children with early childhood neurodegenerative disorder, even in the absence of metabolic crisis. Early evaluation with whole-exome sequencing is useful for early diagnosis and for genetic counseling.