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

研究成果: Article査読

3 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)280-284
ページ数5
ジャーナルBrain and Development
41
3
DOI
出版ステータスPublished - 03-2019

All Science Journal Classification (ASJC) codes

  • 小児科学、周産期医学および子どもの健康
  • 発達神経科学
  • 臨床神経学

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