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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.

Author information

1
Department of Child Neurology, Okayama University Hospital, Okayama, Okayama, Japan. Electronic address: takiyama@okayama-u.ac.jp.
2
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.
3
Japan Clinical Metabolomics Institute, Kahoku, Ishikawa, Japan.
4
Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
5
Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.
6
Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi, Japan.
7
Department of Child Neurology, Okayama University Hospital, Okayama, Okayama, Japan.
8
Department of Neonatology, NHO Okayama Medical Center, Okayama, Okayama, Japan.

Abstract

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.

KEYWORDS:

Inborn error of metabolism; Metabolome analysis; Pyrimidine; Screening

PMID:
27553092
DOI:
10.1016/j.braindev.2016.08.001
[Indexed for MEDLINE]

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