A case of dihydropyrimidinase deficiency incidentally detected by urine metabolome analysis

Hiroki Tsuchiya, Tomoyuki Akiyama, Tomiko Kuhara, Yoko Nakajima, Morimasa Ohse, Hiroki Kurahashi, Takema Kato, Yasuhiro Maeda, Harumi Yoshinaga, Katsuhiro Kobayashi

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Abstract

Dihydropyrimidinase deficiency is a rare autosomal recessive disease affecting the second step of pyrimidine degradation. It is caused by mutations in the DPYS gene. Only approximately 30 cases have been reported to date, with a phenotypical variability ranging from asymptomatic to severe neurological illness. We report a case of dihydropyrimidinase deficiency incidentally detected by urine metabolome analysis. Gas chromatography-mass spectrometry-based urine metabolomics demonstrated significant elevations of dihydrouracil and dihydrothymine, which were subsequently confirmed by a quantitative analysis using liquid chromatography-tandem mass spectrometry. Genetic testing of the DPYS gene revealed two mutations: a novel mutation (c.175G > T) and a previously reported mutation (c.1469G > A). Dihydropyrimidinase deficiency is probably underdiagnosed, considering its wide phenotypical variability, nonspecific neurological presentations, and an estimated prevalence of 2/20,000. As severe 5-fluorouracil-associated toxicity has been reported in patients and carriers of congenital pyrimidine metabolic disorders, urinary pyrimidine analysis should be considered for those who will undergo 5-fluorouracil treatment.

Original languageEnglish
Pages (from-to)280-284
Number of pages5
JournalBrain and Development
Volume41
Issue number3
DOIs
Publication statusPublished - 03-2019

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All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

Tsuchiya, H., Akiyama, T., Kuhara, T., Nakajima, Y., Ohse, M., Kurahashi, H., Kato, T., Maeda, Y., Yoshinaga, H., & Kobayashi, K. (2019). A case of dihydropyrimidinase deficiency incidentally detected by urine metabolome analysis. Brain and Development, 41(3), 280-284. https://doi.org/10.1016/j.braindev.2018.10.005