Phosphoribosylpyrophosphate synthetase superactivity

Phosphoribosylpyrophosphate (PRPP) synthetase superactivity, also known as PRPS1 superactivity, phosphoribosylpyrophosphate synthetase 1 overactivity, or gout due to PRPP synthetase superactivity, is a rare inherited disorder of purine metabolism caused by gain-of-function mutations in the PRPS1 gene. The enzyme PRPP synthetase plays a critical role in purine nucleotide synthesis, and its overactivity leads to excessive production of uric acid (hyperuricemia). This results in the accumulation of uric acid in the blood and tissues, causing a range of clinical problems. The disease primarily affects the musculoskeletal system, kidneys, and nervous system. Key clinical features include early-onset gout (gouty arthritis) with recurrent painful joint inflammation, uric acid kidney stones (urolithiasis), and uric acid nephropathy, which can progress to kidney failure if untreated. The condition presents in two recognized forms: a milder form that typically manifests in late adolescence or early adulthood with gout and kidney stones, and a more severe form that presents in infancy or early childhood with additional neurological features including sensorineural hearing loss, hypotonia, and developmental delay. Some patients may also exhibit neurodevelopmental abnormalities. Treatment focuses on reducing uric acid levels to prevent complications. Allopurinol, a xanthine oxidase inhibitor, is the mainstay of therapy and can effectively lower serum uric acid levels, helping to prevent gout attacks, kidney stones, and renal damage. Adequate hydration and dietary modifications to limit purine intake are also recommended. Early diagnosis and treatment are important to prevent irreversible kidney damage and other complications. Genetic counseling is recommended for affected families.

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