Hyperammonemia after capecitabine associated with occult impairment of the urea cycle.

ABSTRACT:

Background

Cancer patients receiving chemotherapy often complain of "chemobrain" or cognitive impairment, but mechanisms remain elusive.

Methods

A patient with gastric cancer developed delirium and hyperammonemia after chemotherapy with the 5-fluorouracil pro-drug capecitabine. Exome sequencing facilitated a search for mutations among 43 genes associated with hyperammonemia and affecting the urea cycle directly or indirectly.

Results

The patient's urea cycle was impaired by capecitabine-induced liver steatosis, and portosystemic shunting of gut ammonia into the systemic circulation. The patient was also heterozygous for amino acid substitution mutations previously reported to create dysfunctional proteins in 2 genes, ORNT2 (ornithine transporter-2 for the urea cycle),

SUBMITTER: Chu G 

PROVIDER: S-EPMC6536928 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature