A Japanese case of β-ureidopropionase deficiency with dysmorphic features

Brain Dev. 2017 Jan;39(1):58-61. doi: 10.1016/j.braindev.2016.08.001. Epub 2016 Aug 21.


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.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / physiopathology*
  • Amidohydrolases / deficiency*
  • Amidohydrolases / genetics
  • Asians / genetics
  • Brain Diseases / diagnosis*
  • Brain Diseases / genetics
  • Brain Diseases / physiopathology*
  • DNA Mutational Analysis
  • Diagnosis, Differential
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Infant
  • Japan
  • Metabolome*
  • Microarray Analysis
  • Movement Disorders / diagnosis*
  • Movement Disorders / genetics
  • Movement Disorders / physiopathology*
  • Purine-Pyrimidine Metabolism, Inborn Errors / diagnosis*
  • Purine-Pyrimidine Metabolism, Inborn Errors / genetics
  • Purine-Pyrimidine Metabolism, Inborn Errors / physiopathology*
  • Urine / chemistry*


  • Amidohydrolases
  • beta-ureidopropionase

Supplementary concepts

  • Beta-Ureidopropionase Deficiency