LeschNyhan

Lesch-Nyhan syndrome is a rare X-linked recessive metabolic disorder caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), usually due to mutations in the HPRT1 gene. The deficiency impairs purine salvage, increasing de novo purine synthesis and leading to elevated uric acid levels in blood and urine. The condition is generally evident in infancy or early childhood and is characterized by both metabolic and neurological problems.

The extent of HGPRT deficiency correlates with disease severity. Complete deficiency produces the classic Lesch-Nyhan syndrome, while partial deficiency can result in milder or atypical forms. Hyperuricemia commonly causes gout, uric acid stones, and other kidney problems. Neurological and behavioral features are prominent and include dystonia, choreoathetosis, spasticity, and cognitive impairment. A hallmark of the disorder is self-injurious behavior, such as lip and finger biting, which typically begins in early childhood and requires protective strategies and behavioral management.

Diagnosis is based on laboratory and genetic findings. HGPRT enzyme activity is markedly reduced or absent in blood cells or fibroblasts, and genetic testing can identify mutations in the HPRT1 gene. Elevated uric acid and uric acid excretion are common laboratory findings.

There is no cure for Lesch-Nyhan syndrome. Management focuses on reducing uric acid production with allopurinol, ensuring adequate hydration, and minimizing stone formation. Symptomatic treatments address motor symptoms and pain, including physical and occupational therapy, antispastic medications, and protective devices to reduce self-injury. Supportive care, dental management, and multidisciplinary coordination are essential. Prognosis varies; life expectancy is often reduced relative to the general population, and care plans emphasize quality of life and safety.