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.
Keywords
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Article info
Publication history
Published online: October 29, 2018
Accepted:
October 16,
2018
Received in revised form:
September 29,
2018
Received:
August 7,
2018
Identification
Copyright
© 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.