A Japanese case of β-ureidopropionase deficiency with dysmorphic features

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• 作者：Tomoyuki Akiyama^a ; ^{takiyama@okayama-u.ac.jp} ; Takashi Shibata^a ; ^b ; Harumi Yoshinaga^a ; ^b ; Tomiko Kuhara^c ; Yoko Nakajima^d ; Takema Kato^e ; Yasuhiro Maeda^f ; Morimasa Ohse^c ; Makio Oka^a ; Misao Kageyama^g ; Katsuhiro Kobayashi^a ; ^b
• 关键词：Metabolome analysis ; Screening ; Pyrimidine ; Inborn error of metabolism
• 刊名：Brain and Development
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：39
• 期：1
• 页码：58-61
• 全文大小：588 K
• 卷排序：39

文摘

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.