JIMD Reports - Case and Research Reports, 2012/3

Hye-Sook Chang, Takako Shibata, Satoshi Arai, Chunhua Zhang, Akira Yabuki, Sawane Mitani, Takashi Higo, Kazuhiro Sunagawa, Keijiro Mizukami, Osamu Yamato, Chang, Hye-Sook, Shibata, Takako, Arai, Satoshi, Zhang, Chunhua, Yabuki, Akira, Mitani, Sawane, Higo, Takashi, Sunagawa, Kazuhiro, Mizukami, Keijiro, Yamato, Osamu

Dihydropyrimidinase (DHP, EC 3.5.2.2) is the second enzyme of the pyrimidine degradation pathway and a deficiency of this enzyme is responsible for a rare inborn metabolic syndrome characterized by dihydropyrimidinuria. Here we report a cat with DHP deficiency, manifesting malnutrition, depression, vomiting, and hyperammonemia. A gas chromatographic-mass spectrometric analysis of urinary metabolic substances showed the presence of large amounts of dihydrouracil and dihydrothymine and moderate amounts of uracil and thymine, suggesting DHP deficiency. Analysis of the feline DPYS gene encoding DHP demonstrated that the cat was homozygous for the missense mutation c.1303G>A (p.G435R) in exon 8, which corresponds to a known mutation in a human patient with DHP deficiency. Population screening in 1,000 cats did not reveal any animal possessing this mutation, suggesting the prevalence of the mutant allele to be very low. This is the first report of naturally occurring DHP deficiency in animals and the cat represents a model of the human disease.