Common Disorders Related to Nucleotide Metabolism

Lesch-Nyhan Syndrome: Genetic Basis and Neurological Manifestations

Lesch-Nyhan Syndrome (LNS) is a rare, X-linked recessive genetic disorder resulting from mutations in the HPRT1 gene, which encodes the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). The deficiency of this enzyme leads to an accumulation of uric acid, causing severe neurological symptoms and self-injurious behaviors.

Genetic Basis

The HPRT1 gene mutation affects purine salvage pathways, leading to excessive uric acid production. Since the gene is located on the X chromosome, LNS predominantly affects males.

Neurological Manifestations

• Self-mutilation (lip and finger biting)
• Involuntary muscle movements (dystonia, spasticity)
• Cognitive impairments
• Hyperuricemia leading to gout and renal complications

Treatment and Management

Although no cure exists, management focuses on symptomatic treatment, including:

• Allopurinol for uric acid reduction
• Behavioral therapy to manage self-injury
• Physical therapy for motor control improvement

Conclusion

Lesch-Nyhan Syndrome is a devastating disorder requiring a multidisciplinary approach for effective management. Advances in genetic research may provide future therapeutic solutions.