Abstract
A 21-year-old man with sensorineural hearing loss and glaucoma presented with severely limited exercise capacity since childhood. He was found to have biventricular concentric hypertrophy with greatest wall thickening at the posterior and lateral walls of the left ventricle apex (1.7 cm) and the free wall of the right ventricle (1.1 cm). There was no inducible left ventricular outflow tract obstruction. Metabolic testing revealed marked lactic aciduria (1,650.1 μmol/mmol creatinine) and plasma lactate (3.9 mmol/L). A sarcomeric hypertrophic cardiomyopathy gene panel was unremarkable, but mitochondrial gene analysis revealed a homozygous c.385G>A (p.Gly129Arg) pathogenic mutation in the BCS1L gene. This gene is responsible for an assembly subunit of cytochrome complex III in the respiratory transport chain and is the rarest respiratory chain defect. This gene has not frequently been implicated in cardiomyopathy. Mitochondrial hypertrophic cardiomyopathy is more rare than hypertrophic cardiomyopathy resulting from sarcomeric mutations and is more likely to be symmetric, less frequently results in left ventricular outflow tract obstruction, and is more likely to progress to dilated cardiomyopathy. Evidence-based screening protocols have not been established; treatment follows guideline-directed medical therapy for congestive heart failure, including evaluation for heart transplantation. This report expands the phenotype of the BCS1L mutation and suggests that affected patients may need screening for underlying cardiomyopathy.