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Clinical Reasoning: A Young Adult Man With Cognitive Changes, Gait Difficulty, and Renal Insufficiency.

A 22-year-old right-handed man with recently diagnosed gout and renal insufficiency presented with three months of progressive gait instability and cognitive changes. He initially presented to an outside institution and underwent a broad workup, but an etiology for his symptoms was not found. On subsequent presentation to our institution, his exam revealed multi-domain cognitive dysfunction, spasticity, hyperreflexia and clonus. A broad workup was again pursued and was notable for an MRI of the brain revealing cortical atrophy advanced for his age, bland cerebrospinal fluid, and a weakly positive serum acetylcholine receptor ganglionic neuronal antibody of unclear significance. The history of gout and inadequately explained renal insufficiency led to a workup for inborn errors of metabolism, including urine amino acid analysis, which revealed a homocysteine peak. This finding prompted further evaluation, revealing markedly elevated serum homocysteine and methylmalonic acid and low methionine. He ultimately developed superficial venous thromboses and a segmental pulmonary embolism, as well as clinical and electrographic seizures. He was initiated on appropriate treatment, and his symptoms markedly improved. The case serves as a reminder to include late-onset inborn errors of metabolism in the differential for young adult patients with onset of neurological, psychiatric, renal, and thromboembolic symptoms.