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Brain Dev. 2017 Jan;39(1):58-61. doi: 10.1016/j.braindev.2016.08.001. Epub 2016 Aug 21.

A Japanese case of β-ureidopropionase deficiency with dysmorphic features.

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Department of Child Neurology, Okayama University Hospital, Okayama, Okayama, Japan. Electronic address:
Department of Child Neurology, Okayama University Hospital, Okayama, Okayama, Japan; Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama, Japan.
Japan Clinical Metabolomics Institute, Kahoku, Ishikawa, Japan.
Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.
Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi, Japan.
Department of Child Neurology, Okayama University Hospital, Okayama, Okayama, Japan.
Department of Neonatology, NHO Okayama Medical Center, Okayama, Okayama, Japan.


β-Ureidopropionase deficiency is a rare autosomal recessive disease affecting the last step of pyrimidine degradation, and it is caused by a mutation in the UPB1 gene. Approximately 30 cases have been reported to date, with a phenotypical variability ranging from asymptomatic to severe neurological illness. Non-neurological symptoms have been rarely reported. We describe a case of this disease with developmental delay and dysmorphic features. Gas chromatography-mass spectrometry-based urine metabolomics demonstrated significant (⩾+4.5 standard deviation after logarithmic transformation) elevations of β-ureidopropionic acid and β-ureidoisobutyric acid, strongly suggesting a diagnosis of β-ureidopropionase deficiency. Subsequent quantitative analysis of pyrimidines by liquid chromatography-tandem mass spectrometry supported this finding. Genetic testing of the UPB1 gene confirmed compound heterozygosity of a novel mutation (c.976C>T) and a previously-reported mutation (c.977G>A) that is common in East Asians. β-Ureidopropionase deficiency is probably underdiagnosed, considering a wide phenotypical variability, non-specific neurological presentations, and an estimated prevalence of 1/5000-6000. Urine metabolomics should be considered for patients with unexplained neurological symptoms.


Inborn error of metabolism; Metabolome analysis; Pyrimidine; Screening

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