ABSTRACT
Hyperuricemia, uricosuria, hematuria, crystalluria, urinary tract calculi, gouty arthritis, nephropathy, sensorineural deafness, and abnormal phosphoribosylpyrophosphate (PRPP) synthetase, in which activity is greater than normal. Moderate deficiency of activity of PRPP synthetase and mutations in PRPS1 were found in patients with a triad of peripheral neuropathy, hypotonia, and deafness. The relationship of all of the problems to the metabolic abnormality is not clear, but the mother also had the abnormal PRPP synthetase and hearing loss, and she and her father had problems with behavior. Missense mutations in PRPPS and mild deficiency of activity of the enzyme are found in patients with X-linked nonsyndromes features deafness. The molecular basis of the disease in the patients with superactive enzyme activity is an altered PRPP synthetase structure. Pathogenesis has been related to low levels of the important nucleotide guanosine triphosphate which is essential for G-protein function and synthesis of dopamine and pterins in brain.
