Lesch-Nyhan syndrome

Lesch-Nyhan syndrome is a severe hereditary disorder of purine metabolism caused by pathogenic variants in the HPRT1 gene. The resulting enzyme deficiency leads to an overproduction of uric acid and affects the nervous system, manifesting as neurological and behavioral abnormalities. Most affected individuals are males who present in early childhood with developmental delays and cognitive challenges. This condition is rare, affecting approximately 1 to 9 per million people.

Individuals with Lesch-Nyhan syndrome typically present with global developmental delay, intellectual disability, and hypotonia, all of which are consistently observed. Additional features include hyperuricemia, poor head control, and self-injurious behavior, which occurs in most cases. Some affected individuals may also develop complications such as nephrocalcinosis, seizures, or hip dislocation. Not all individuals experience all features, and severity varies considerably.

Lesch-Nyhan syndrome results from pathogenic variants in the HPRT1 gene, which encodes the enzyme hypoxanthine-guanine phosphoribosyltransferase that plays a key role in purine metabolism. The deficiency of this enzyme disrupts normal purine recycling and leads to excess uric acid production. Inherited in an X-linked recessive pattern, the condition primarily affects males, while female carriers may experience mild symptoms due to skewed X-inactivation and should discuss monitoring with their healthcare provider. Genetic counseling is recommended to help families understand inheritance and family planning options.

Currently, management focuses on supportive care and symptom management, with treatment tailored to the unique needs of each patient. A multidisciplinary team typically addresses the neurological, behavioral, and metabolic aspects of Lesch-Nyhan syndrome. Although there are no FDA-approved or foundational therapies specific to this condition, regular monitoring and supportive interventions can help manage complications. Genetic counseling is recommended, and patients should discuss available treatment options with their healthcare team to determine the most appropriate approach.

Lesch-Nyhan syndrome is a lifelong neurodevelopmental condition marked by considerable variability in severity and symptom presentation. Outcomes vary depending on the intensity of symptoms, age at diagnosis, and access to specialized care, with many individuals living into adulthood under current care standards. Outcomes described in medical literature continue to evolve as standards of care improve, reinforcing the importance of ongoing monitoring and individualized management. Families often find it helpful to connect with specialists experienced in neurodevelopmental disorders and to consider genetic counseling for further guidance.

Several clinical trials are currently exploring new treatment approaches for Lesch-Nyhan syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.