When rare diseases do not appear as a single entity

Abstract

Abstract Objectives The coexistence of multisystemic involvement in a young adult raises the need to consider rare metabolic and mitochondrial disorders. We report a case of late-onset propionic acidemia (PPA) that may have contributed to unmasking Leber hereditary optic neuropathy (LHON), an extremely infrequent association. Case presentation A 43-year-old woman presented with acute biventricular heart failure following a viral infection. Evaluation revealed severe dilated cardiomyopathy, newly diagnosed type 2 diabetes mellitus, and bilateral sensorineural hearing loss. Genetic testing for cardiomyopathy was unremarkable. Two months later, she developed sudden bilateral blindness due to optic neuropathy. Extended genetic analysis identified a pathogenic RDH12 variant consistent with LHON and two POLG variants. Progressive renal dysfunction and long QTc interval prompted metabolic investigation. Urine organic acids showed marked accumulation of propionate-related metabolites, and plasma acylcarnitines revealed elevated C3 and low free carnitine, confirming late-onset PPA. The pattern of cardiac dysfunction, renal impairment, and hearing loss was consistent with chronic multisystem toxicity of PPA. Conclusions In this patient, mitochondrial dysfunction from PPA may have precipitated the clinical expression of LHON, a condition with incomplete penetrance. This exceptional coexistence highlights that rare diseases may overlap and that unexplained multisystem findings warrant comprehensive metabolic and genetic evaluation.