Purine salvage defects Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) leads to which inherited disorder?
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AGaucher’s disease
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BEhlers–Danlos syndrome
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CLesch–Nyhan syndrome
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DKlinefelter’s syndrome
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EMarfan syndrome
Answer
Correct Answer: Lesch–Nyhan syndrome
Explanation
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:
Identify pathway: purine salvage via HGPRT.Link deficiency to hallmark signs: gouty tophi, neurologic symptoms, self-mutilation.Select the named disorder: Lesch–Nyhan syndrome.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