LESCH-NYHAN SYNDROME: PATHOPHYSIOLOGY, CLINICAL MANIFESTATIONS, AND EMERGING THERAPEUTIC APPROACHES

Abstract

Lesch-Nyhan Syndrome is a rare X-linked recessive genetic disorder caused by mutations in the HPRT1 gene, which codes for the enzyme hypoxanthine-guanine phosphoribosyl transferase (HPRT). This enzyme is necessary for the purine salvage pathway, which recycles purines to keep the cells' nucleotide equilibrium. Excess uric acid and other serious neurological and behavioral issues are caused by a lack of HPRT activity. Clinical signs of Lesch-Nyhan Syndrome include hyperuricemia, gout, kidney stones, cognitive impairment, motor dysfunction (including stiffness and dystonia), and a characteristic conduct that is self-harming, such as biting one's lips or fingers. The condition primarily affects men due to its X-linked inheritance pattern. Since there is currently no known cure for Lesch-Nyhan Syndrome, supportive care is the cornerstone of treatment to lower neurological symptoms and regulate uric acid levels. Current research is looking into gene therapy and enzyme substitution as potential treatment modalities. Early diagnosis using enzymatic assays and genetic testing is essential for family counselling and disease management. Early diagnosis using enzymatic assays and genetic testing is essential for family counselling and disease management. Treatment is centered on managing symptoms because there is currently no cure. Neurological and behavioral problems are treated with medicine and supportive care, while uric acid levels are controlled with allopurinol. Purine metabolism and the neurological effects of metabolic dysregulation have been better understood because of our growing understanding of the molecular groundwork of Lesch-Nyhan Syndrome.