A Case of Hyperammonemia Associated with High Dihydropyrimidine Dehydrogenase Activity

Abstract

Over the past decades, 5-Fluorouracil (5-FU) has been widely used to treat several types of carcinoma, including esophageal squamous cell carcinoma. In addition to its common side effects, including diarrhea, mucositis, neutropenia, and anemia, 5-FU treatment has also been reported to cause hyperammonemia. However, the exact mechanism responsible for 5-FU-induced hyperammonemia remains unknown. We encountered an esophageal carcinoma patient who developed hyperammonemia when receiving 5-FU-containing chemotherapy but did not exhibit any of the other common adverse effects of 5-FU treatment. At the onset of hyperammonemia, laboratory tests revealed high dihydropyrimidine dehydrogenase (DPD) activity and rapid 5-FU clearance. Our findings suggested that 5-FU hypermetabolism may be one of the key mechanisms responsible for hyperammonemia during 5-FU treatment.

A case of acute hyperammonemic encephalopathy after initiation of 5-fluorouracil chemotherapy

“…[7] Although there are insufficient data on the relationship between DPD activity and hyperammonemic encephalopathy, there are case reports of hyperammonemic encephalopathy occurring in patients with both partial and complete DPD deficiencies and in patients with elevated DPD activity suggesting that, further, research is needed in this area. [3,8,9] Once diagnosed, there are no clear guidelines for management of 5-FU-induced hyperammonemic encephalopathy. It is generally managed with 5-FU discontinuation and administration of ammonialowering therapies including lactulose, low-protein diet, renal replacement, and ammonium chelators.…”