From sarcopenia to a genetic diagnosis: Exercise- induced weakness and androgen insensitivity unmasking Kenedy’s disease

Abstract

Spinal and bulbar muscular atrophy, or Kennedy’s disease, is a rare, X-linked neurodegenerative disorder often misdiagnosed due to its mimicry of common musculoskeletal conditions. Diagnostic delay is typical, averaging five years. A 46-year-old male presented with a three-year history of progressive, exertional lower limb weakness and buttock pain following a minor fall. Extensive evaluations for lumbosacral radiculopathy, piriformis syndrome, peripheral arterial disease, and tendinopathy were unremarkable. Key examination findings included subtle fasciculations, and hyporeflexia, with absent of obvious atrophy. Serial bioimpedance analysis objectively demonstrated an inability to accrue skeletal muscle mass despite dedicated rehabilitation. The critical diagnostic inflection point was the recognition of previously overlooked signs of androgen insensitivity: gynecomastia and long-standing erectile dysfunction with retrograde ejaculation. This constellation of findings prompted genetic testing, which confirmed a pathologic CAG repeat expansion (48 repeats) in the androgen receptor (AR) gene. This case underscores that in males with progressive lower motor neuron symptoms, the presence of endocrine features even subtle or long-standing is paramount to distinguishing spinal and bulbar muscular atrophy from its mimics. Unexplained, exertional weakness with objective evidence of neurogenic atrophy on body impedance analysis should elevate clinical suspicion. A holistic review of systems and signs is essential to shortening the diagnostic odyssey in rare neurological diseases.