RESUMO
OBJECTIVE: The objective of this study was to analyze the diagnosis of HPRT deficiency, perform a thorough purine metabolism study and to establish the carrier and prenatal diagnosis in 16 HPRT deficient families. PATIENTS AND METHODS: Plasma and urinary concentrations of uric acid, creatinine and oxypurines, APRT and HPRT activities in hemolysates and HPRT in intact erythrocytes and adenine 8-C14 urinary excretion were analyzed. Carrier diagnosis was made by hair root enzyme analysis and genetic studies. RESULTS: These studies allowed the diagnosis of HPRT deficiency in 20 patients. Carrier diagnosis could be performed in 23 women at risk and in a 9 week old female fetus. CONCLUSIONS: The study results suggest that HPRT deficiency accounts for increased purine nucleotide degradation. This increase results in elevated urinary and plasma concentrations of hypoxanthine, xanthine and uric acid. The clinical severity of the disease is not related to the degree of urinary or plasma concentrations of oxypurines. Hair root analysis generally allows the diagnosis of carrier status, but the carrier state cannot be fully excluded in women at risk. When the familial mutation causing the defect in HPRT is known, analysis of the differences in the restriction pattern of the HPRT gene (natural or due to directed mutagenesis) allow a rapid and reliable diagnosis of carrier status and HPRT deficiency.
