Adv Lab Med. 2026 Jul 16;7(3):234-237. doi: 10.1515/almed-2025-0193. eCollection 2026 Sep.
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.
PMID:42713573 | PMC:PMC13552808 | DOI:10.1515/almed-2025-0193