A Japanese case of β-ureidopropionase deficiency with dysmorphic features

Tomoyuki Akiyama, Takashi Shibata, Harumi Yoshinaga, Tomiko Kuhara, Yoko Nakajima, Takema Kato, Yasuhiro Maeda, Morimasa Ohse, Makio Oka, Misao Kageyama, Katsuhiro Kobayashi

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)58-61
Number of pages4
JournalBrain and Development
Volume39
Issue number1
DOIs
Publication statusPublished - 01-01-2017

Fingerprint

Metabolomics
Mutation
Urine
Pyrimidines
Acids
Genetic Testing
Genes
Mass Spectrometry
Spectrum Analysis
Gases
pyrimidine

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

Akiyama, T., Shibata, T., Yoshinaga, H., Kuhara, T., Nakajima, Y., Kato, T., ... Kobayashi, K. (2017). A Japanese case of β-ureidopropionase deficiency with dysmorphic features. Brain and Development, 39(1), 58-61. https://doi.org/10.1016/j.braindev.2016.08.001
Akiyama, Tomoyuki ; Shibata, Takashi ; Yoshinaga, Harumi ; Kuhara, Tomiko ; Nakajima, Yoko ; Kato, Takema ; Maeda, Yasuhiro ; Ohse, Morimasa ; Oka, Makio ; Kageyama, Misao ; Kobayashi, Katsuhiro. / A Japanese case of β-ureidopropionase deficiency with dysmorphic features. In: Brain and Development. 2017 ; Vol. 39, No. 1. pp. 58-61.
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Akiyama, T, Shibata, T, Yoshinaga, H, Kuhara, T, Nakajima, Y, Kato, T, Maeda, Y, Ohse, M, Oka, M, Kageyama, M & Kobayashi, K 2017, 'A Japanese case of β-ureidopropionase deficiency with dysmorphic features', Brain and Development, vol. 39, no. 1, pp. 58-61. https://doi.org/10.1016/j.braindev.2016.08.001

A Japanese case of β-ureidopropionase deficiency with dysmorphic features. / Akiyama, Tomoyuki; Shibata, Takashi; Yoshinaga, Harumi; Kuhara, Tomiko; Nakajima, Yoko; Kato, Takema; Maeda, Yasuhiro; Ohse, Morimasa; Oka, Makio; Kageyama, Misao; Kobayashi, Katsuhiro.

In: Brain and Development, Vol. 39, No. 1, 01.01.2017, p. 58-61.

Research output: Contribution to journalArticle

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AU - Akiyama, Tomoyuki

AU - Shibata, Takashi

AU - Yoshinaga, Harumi

AU - Kuhara, Tomiko

AU - Nakajima, Yoko

AU - Kato, Takema

AU - Maeda, Yasuhiro

AU - Ohse, Morimasa

AU - Oka, Makio

AU - Kageyama, Misao

AU - Kobayashi, Katsuhiro

PY - 2017/1/1

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N2 - 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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