| An X-linked disorder of purine metabolism comprised of two forms: an early-onset severe form with characteristics of gout, urolithiasis, and neurodevelopmental anomalies (severe PRPP synthetase superactivity) and a mild late-onset form with no neurologic involvement (mild PRPP synthetase superactivity).The disease is due to overactivity of ribose-phosphate pyrophosphokinase 1 (PRS-I), an enzyme involved in the synthesis of PRPP, a cofactor involved in the synthesis of purine and pyrimidine nucleotides. PRS-I overactivity results in the overproduction of purine nucleotides and uric acid. In the severe form, PRS-I overactivity is due to gain-of-function point mutations in the open reading frame of the PRSP1 gene (Xq22.3) encoding PRS-I, that lead to defective allosteric control of PRS-I isoform activity. |
