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

Research output: Contribution to journalArticle


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
JournalBrain and Development
Publication statusAccepted/In press - Jan 1 2018



  • 5-Fluorouracil
  • DPYS gene
  • Pyrimidine metabolism
  • Screening

ASJC Scopus subject areas

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

Cite this