Definition: inherited genetic disorder characterized by impaired purine salvage pathway, resulting in an overproduction of uric acid

Epidemiology

Etiology

Pathophysiology

Defect in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) → impaired conversion of hypoxanthine to IMP and guanine to GMP → excess uric acid and ↑ de novo purine synthesis

Clinical features

• Usually asymptomatic for the first 6 months of life
• Orange sand-like sodium urate crystals can be found in the diapers of infants with hyperuricemia.
  • See Nephrolithiasis#Uric acid stones
• Developmental delay and cognitive impairment
• Pyramidal and extrapyramidal symptoms (e.g., dystonia, spasticity)
• Gouty arthritis, urate nephropathy
  • Due to the accumulation of uric acid in peripheral tissues
• Aggression, self-injurious behavior
  • E.g., finger chewing, lip biting, headbanging
• Renal failure

Diagnostics

• Hyperuricemia
• ↓ HGPRT activity
• ↑ Phosphoribosyl pyrophosphate amidotransferase (converts PRPP to GMP and AMP)
• Macrocytosis (megaloblastic anemia may occur)

Treatment

• Reduce uric acid levels:
  • Allopurinol (first-line)
  • Febuxostat (second-line)
  • Low-purine diet