RESUMO
Dihydropyrimidinase (DHP) deficiency is an inborn error of the pyrimidine degradation pathway, affecting the hydrolytic ring opening of the dihydropyrimidines. In two siblings with a complete DHP deficiency and a variable clinical presentation, a normal concentration of beta-alanine and strongly decreased levels of beta-aminoisobutyric acid were observed in plasma, urine and CSF. No major differences were observed for the concentrations of the beta-amino acids in plasma and urine between the symptomatic and asymptomatic sibling. Thus, the relevance of the shortage of beta-aminoisobutyric acid for the onset of a clinical phenotype in patients with DHP deficiency remains to be established.
Assuntos
Amidoidrolases/deficiência , Ácidos Aminoisobutíricos/metabolismo , Irmãos , beta-Alanina/metabolismo , Amidoidrolases/genética , Amidoidrolases/metabolismo , Ácidos Aminoisobutíricos/sangue , Ácidos Aminoisobutíricos/líquido cefalorraquidiano , Ácidos Aminoisobutíricos/urina , Humanos , beta-Alanina/sangue , beta-Alanina/líquido cefalorraquidiano , beta-Alanina/urinaRESUMO
Dihydropyrimidine dehydrogenase (DPD) constitutes the first step of the pyrimidine degradation pathway in which the pyrimidine bases uracil and thymine are catabolised to beta-alanine and beta-aminoisobutyric acid (beta-AIB), respectively. The mean concentration of beta-AIB was approximately 5- to 8-fold lower in urine of patients with a DPD deficiency, when compared to age-matched controls. Comparable levels of 8-hydroxydeoxyguanosine (8-OHdG) were present in urine from controls and DPD patients at the age <2 year. In contrast, slightly elevated levels of 8-OHdG were detected in urine from DPD patients with an age >2 year, suggesting the presence of increased oxidative stress.
