无症状的
复合杂合度
杂合子丢失
尿
突变
医学
代谢组学
疾病
表型
遗传学
儿科
等位基因
内科学
生物
基因
生物信息学
作者
Tomoyuki Akiyama,Takashi Shibata,Harumi Yoshinaga,Tomiko Kuhara,Yoko Nakajima,Takema Kato,Yasuhiro Maeda,Morimasa Ohse,Makio Oka,Misao Kageyama,Katsuhiro Kobayashi
标识
DOI:10.1016/j.braindev.2016.08.001
摘要
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.
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