The clinical presentation of inborn errors of pyrimidine degradation varies considerably from asymptomatic to severe neurological illness. We have reported a method to screen for and make a chemical diagnosis of beta-ureidopropionase deficiency, leading to the discovery of the first asymptomatic case of this disease. In this method, the recovery of beta-ureidopropionate and beta-ureidoisobutyrate, the key biomarkers, was very high,and the adoption of GC/MS and targeted analysis enabled us to simultaneously obtain information related and unrelated to pyrimidine metabolism. The present study reports the results of a large-scale screening of 24,000 newborns using dried urine on filter paper. Identification of a total of four asymptomatic patients among newborns suggests the high incidence (1/6000) of this disease in Japan. While these newborns were asymptomatic, two additional cases detected at the age of 5 years as well as 3 months with this method for high-risk screening had autism and West syndrome, respectively.The key biomarkers and alpha-ureidobutyrate used as an internal standard were found to give not only their di-trimethylsilyl derivatives but also tri-trimethylsilyl derivatives, upon derivatization. The mass spectra and retention times of their tri-trimethylsilyl derivatives and data handling for quantification of the markers are presented.Identification of individuals with defects in pyrimidine metabolism would realize personalized medication in cancer chemotherapy with pyrimidine analogs such as 5-fluorouracil.
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The relationship between beta-ureidopropionase deficiency due to UPB1 variants and human phenotypes is uncertain.
Mol Genet Metab
January 2023
University of New South Wales, Sydney, NSW, Australia; Sydney Children's Hospitals Network, Sydney, NSW, Australia; New South Wales Health Pathology, Sydney, NSW, Australia. Electronic address:
Background: Beta-ureidopropionase deficiency, caused by variants in UPB1, has been reported in association with various neurodevelopmental phenotypes including intellectual disability, seizures and autism.
Aim: We aimed to reassess the relationship between variants in UPB1 and a clinical phenotype.
Methods: Literature review, calculation of carrier frequencies from population databases, long-term follow-up of a previously published case and reporting of additional cases.
Background: β-Ureidopropionase deficiency is a rare autosomal recessive disease affecting the last step of pyrimidine degradation. Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare inherited disorder caused by genetic defects in mitochondrial DNA.
Case Presentation: One 8-year-old boy presented with dizziness, vomiting, and convulsions.
β-Ureidopropionase deficiency due to novel and rare UPB1 mutations affecting pre-mRNA splicing and protein structural integrity and catalytic activity.
Mol Genet Metab
July 2022
Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, Laboratory Genetic Metabolic Diseases, Amsterdam, the Netherlands. Electronic address:
β-Ureidopropionase is the third enzyme of the pyrimidine degradation pathway and catalyses the conversion of N-carbamyl-β-alanine and N-carbamyl-β-aminoisobutyric acid to β-alanine and β-aminoisobutyric acid, ammonia and CO. To date, only a limited number of genetically confirmed patients with a complete β-ureidopropionase deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 10 newly identified β-ureidopropionase deficient individuals.
View Article and Find Full Text PDFClinical and genetic analysis of 7 Chinese patients with β-ureidopropionase deficiency.
Medicine (Baltimore)
January 2019
Institution of Pediatrics.
β-Ureidopropionase (βUP) deficiency is an autosomal recessive disease caused by abnormal changes in the pyrimidine-degradation pathway. This study aimed to investigate the mutation of β-ureidopropionase gene (UPB1) gene and clinical features of 7 Chinese patients with βUP deficiency.We reported 7 Chinese patients with βUP deficiency who were admitted at Tianjin Children's Hospital.
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