Abstract
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.
Competing interests: None declared
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Acknowledgments
This study was supported financially by grants (20380173, 20-08112, and 21658109, O.Y.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Communicated by: Marinus Duran
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This is the first report of naturally occurring dihydropyrimidinase deficiency in animals and the cat represents a model of the human disease.
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© 2012 SSIEM and Springer-Verlag Berlin Heidelberg
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Chang, HS. et al. (2012). Dihydropyrimidinase Deficiency: The First Feline Case of Dihydropyrimidinuria with Clinical and Molecular Findings. In: JIMD Reports - Case and Research Reports, 2012/3. JIMD Reports, vol 6. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2012_139
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DOI: https://doi.org/10.1007/8904_2012_139
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