Fulminant hyperammonemia during intensive chemotherapy in the setting of previously unrecognized partial ornithine transcarbamylase deficiency.

Hyperammonemic encephalopathy is a rare but often fatal complication in patients with hematological malignancies receiving intensive therapy, and its underlying mechanism is often unclear. We report the case of a woman in her 40 s with acute myeloid leukemia who developed fulminant nonhepatic hyperammonemia during high-dose cytarabine consolidation in association with previously unrecognized partial ornithine transcarbamylase (OTC) deficiency. On day 5 of consolidation, she developed rapidly progressive altered consciousness with marked hyperammonemia, preserved hepatic and renal function, and no evidence of active sepsis. Brain magnetic resonance imaging showed cortical abnormalities more consistent with metabolic encephalopathy than cytarabine-associated neurotoxicity or posterior reversible encephalopathy syndrome. Despite supportive therapy, serum ammonia increased further, followed by seizures, diffuse cerebral edema, and death. Metabolic evaluation suggested a urea cycle disorder, and genetic testing identified a heterozygous pathogenic OTC variant, indicating an underlying inherited metabolic predisposition. Reported adult cases of severe nonhepatic hyperammonemia in hematological malignancies have largely been considered idiopathic or infection-related, whereas genetically confirmed urea cycle disorders remain rare. This case expands the spectrum of chemotherapy-associated nonhepatic hyperammonemia and suggests that occult inherited metabolic predisposition may contribute to its pathogenesis, highlighting the importance of early recognition of hyperammonemia in unexplained encephalopathy during intensive chemotherapy.