Genetic analysis of the first 4 patients with beta-ureidopropionase deficiency.

β-Ureidopropionase is the third enzyme of the pyrimidine degradation pathway and it catalyses the irreversible hydrolysis of N-carbamyl-s-aminoisobutyric acid or N-carbamyl-s-alanine to β-aminoisobutyric acid or s-alanine, ammonia, and CO2. Analysis of the β-ureidopropionase gene (UPB1) of the first 4 patients presenting with a complete enzyme deficiency, revealed the presence of 2 splice-site mutations (IVS1-2A>G and IVS8-1G>A) and one missense mutation (A85E). RT-PCR analysis of the complete β-ureidopropionase cDNA suggested that both splice-site mutations lead to a variety of alternative splice variants, with deletions of a single or several exons. The alanine at position 85 was not conserved in other eukaryotic β-ureidopropionase protein sequences.