Common Disorders Related to Nucleotide Metabolism

HGPRT Deficiency and Its Metabolic Consequences

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency is a genetic disorder that significantly impacts purine metabolism. This enzyme plays a crucial role in the salvage pathway of purines, and its deficiency leads to excessive uric acid production, resulting in various clinical manifestations.

Etiology and Pathophysiology

HGPRT deficiency arises due to mutations in the HPRT1 gene, located on the X chromosome. The condition leads to increased purine degradation and uric acid accumulation, causing hyperuricemia and associated complications.

Clinical Manifestations

• Lesch-Nyhan Syndrome: Severe form characterized by neurological dysfunction, self-mutilation behaviors, and gout.
• Gout: Excess uric acid crystallizes in joints, leading to inflammatory arthritis.
• Kidney Stones: Uric acid precipitation can lead to nephrolithiasis.

Diagnosis and Treatment

Diagnosis involves genetic testing, enzyme activity assays, and uric acid level assessment. Management includes allopurinol to reduce uric acid production and supportive care for neurological symptoms.