Adolescent Hypertrophic Cardiomyopathy Can Be the First Clue to Multisystem Mitochondrial Disease

Up to 40% of children with mitochondrial disease develop hypertrophic cardiomyopathy (HCM) during their disease course, but HCM is almost never the first presenting manifestation. When it is, the underlying mitochondrial disorder is easily missed: the cardiomyopathy is managed in isolation, and extracardiac findings that emerge later may be dismissed as unrelated. We describe an adolescent whose severe HCM was the first major manifestation of clinicopathologically confirmed multisystem mitochondrial disease with a phenotype consistent with Leber hereditary optic neuropathy. Her cardiomyopathy was managed in isolation for over a year before optic atrophy, primary ovarian insufficiency, osteopenia, and exercise intolerance were ultimately recognized as part of a single mitochondrial process. Endomyocardial and skeletal muscle biopsy confirmed mitochondrial pathology. The diagnosis directly changed management: cofactor supplementation was initiated, her visual acuity stabilized on idebenone, and perioperative planning for transplantation was adapted to prevent catabolic decompensation. Her cardiac disease progressed to heart failure requiring transplantation at age 16 years, but she remains clinically stable with preserved graft function more than 15 years later. This case challenges the assumption that mitochondrial disease should enter the differential only after neurologic dysfunction appears. General pediatricians, who see the whole child longitudinally, are uniquely positioned to recognize when dysfunction in other high-energy tissues points toward a unifying mitochondrial diagnosis in a child with cardiomyopathy.