Hypoxanthine-guanine phosphoribosyltransferase deficiency

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT or HPRT) deficiency is an X-linked inherited disorder of purine metabolism caused by mutations in the HPRT1 gene located on the X chromosome. This enzyme plays a critical role in the purine salvage pathway, which recycles purines for reuse in DNA and RNA synthesis. Deficiency of this enzyme leads to accumulation of uric acid in the body, resulting in hyperuricemia and its associated complications. The clinical spectrum of HPRT deficiency ranges from partial deficiency (known as Kelley-Seegmiller syndrome) to complete deficiency (known as Lesch-Nyhan syndrome). In partial deficiency, patients typically present with gout, uric acid nephrolithiasis (kidney stones), and sometimes mild neurological features. Complete deficiency (Lesch-Nyhan syndrome, Orphanet 510) presents with severe neurological involvement including intellectual disability, dystonia, choreoathetosis, and the hallmark feature of compulsive self-injurious behavior such as lip and finger biting. The condition predominantly affects males, while females are typically carriers who are usually asymptomatic. The body systems primarily affected include the musculoskeletal system (gouty arthritis), the renal system (uric acid stones and nephropathy), and the central nervous system (movement disorders and behavioral abnormalities in more severe forms). Treatment includes allopurinol or febuxostat to reduce uric acid levels and prevent gout and renal complications. However, no effective treatment currently exists for the neurological and behavioral manifestations of the severe form. Supportive management includes physical therapy, behavioral interventions, and protective measures to prevent self-injury. Adequate hydration and alkalinization of urine may help prevent kidney stone formation.

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