Purine salvage defects Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) leads to which inherited disorder?

Introduction / Context:HGPRT is a key enzyme in the purine salvage pathway, recycling hypoxanthine and guanine to IMP and GMP. Its deficiency disrupts nucleotide balance and elevates uric acid production.

Given Data / Assumptions:

• X-linked recessive inheritance pattern.
• Clinical triad includes hyperuricemia, neurologic dysfunction, and self-injurious behavior.

Concept / Approach:Without HGPRT, purine bases are degraded rather than salvaged, increasing uric acid and reducing purine nucleotide availability in certain tissues. The classic syndrome is Lesch–Nyhan.

Step-by-Step Solution:

Verification / Alternative check:Biochemical assays show absent or reduced HGPRT activity; genetic testing reveals HPRT1 mutations on X chromosome.

Why Other Options Are Wrong:

• Gaucher: glucocerebrosidase deficiency (lysosomal storage), not purine salvage.
• Ehlers–Danlos: collagen defects.
• Klinefelter’s: sex chromosome aneuploidy (47,XXY).
• Marfan: fibrillin-1 mutation.

Common Pitfalls:Confusing gout from overproduction with specific salvage enzyme deficiencies; Lesch–Nyhan is distinct due to neurological features.

Final Answer:Lesch–Nyhan syndrome