title: A Japanese case of β-ureidopropionase deficiency with dysmorphic features.
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.
authors.affiliation: Department of Child Neurology, Okayama University Hospital, Okayama, Okayama, Japan. Electronic address: takiyama@okayama-u.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: 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.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shibata
authors.affiliation: 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.
authors.forename: Harumi
authors.initials: H
authors.lastname: Yoshinaga
authors.affiliation: Japan Clinical Metabolomics Institute, Kahoku, Ishikawa, Japan.
authors.forename: Tomiko
authors.initials: T
authors.lastname: Kuhara
authors.affiliation: Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakajima
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Takema
authors.initials: T
authors.lastname: Kato
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.affiliation: Japan Clinical Metabolomics Institute, Kahoku, Ishikawa, Japan.
authors.forename: Morimasa
authors.initials: M
authors.lastname: Ohse
authors.affiliation: Department of Child Neurology, Okayama University Hospital, Okayama, Okayama, Japan.
authors.forename: Makio
authors.initials: M
authors.lastname: Oka
authors.affiliation: Department of Neonatology, NHO Okayama Medical Center, Okayama, Okayama, Japan.
authors.forename: Misao
authors.initials: M
authors.lastname: Kageyama
authors.affiliation: 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.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D000581:Amidohydrolases / Q000172:deficiency* / Q000235:genetics; D044466:Asian People / Q000235:genetics; D001927:Brain Diseases / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007223:Infant; D007564:Japan; D055442:Metabolome; D046228:Microarray Analysis; D009069:Movement Disorders / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D014556:Urine / Q000737:chemistry*
chemical_list: D000581:Amidohydrolases; C021590:beta-ureidopropionase
keywords: Inborn error of metabolism; Metabolome analysis; Pyrimidine; Screening