A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A mother brings her son to the pediatrician because she is concerned about his health. She states that throughout her child's life he has demonstrated aggressive behavior. However, he has recently begun biting himself causing injury and bleeding. The patient has a past medical history of mental retardation and episodes of severe joint pain. His temperature is 99.5°F (37.5°C), blood pressure is 87/48 mmHg, pulse is 90/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam reveals a child attempting to bite his arms. Which of the following is the inheritance pattern of the disease with which this patient presents?
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A
Autosomal recessiveIncorrect. Autosomal recessive disorders (e.g., PKU) do not show the male predominance and X-linked inheritance pattern seen in Lesch-Nyhan.
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B
MaternalIncorrect. Maternal (mitochondrial) inheritance affects both sexes and presents with neuromuscular and metabolic manifestations (MELAS, LHON), not gout and self-mutilation.
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C
X-linked dominantIncorrect. X-linked dominant disorders affect females more often (e.g., Alport, fragile X has dominant features); Lesch-Nyhan is recessive.
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D
X-linked recessiveCorrect. The HPRT1 gene is on the X chromosome, so HGPRT deficiency (Lesch-Nyhan syndrome) is X-linked recessive and affects males.
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E
Autosomal dominantIncorrect. Autosomal dominant disorders (e.g., Huntington, Marfan) affect both sexes equally; Lesch-Nyhan is X-linked recessive with near-exclusive male involvement and would not fit a dominant pattern.
↑ Tap an answer to reveal the reasoning
Answer: D. A boy with intellectual disability, self-mutilation (biting his arms), aggression, and episodes of severe joint pain (gout) has Lesch-Nyhan syndrome. Lesch-Nyhan is caused by complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), the salvage enzyme that recycles hypoxanthine and guanine. Without salvage, purines are funneled into uric acid, producing hyperuricemia, gout, and uric-acid kidney stones from early childhood. The neurologic phenotype includes intellectual disability, choreoathetosis/dystonia, and characteristically severe self-injurious behavior (lip and finger biting).
The HPRT1 gene is on the X chromosome, making Lesch-Nyhan an X-linked recessive disorder. It affects boys, who inherit the defective allele from carrier mothers. Treatment with allopurinol reduces uric-acid complications but does not improve the neurologic phenotype.
Pearl mnemonic for Lesch-Nyhan: "He's Got Purine Recovery Trouble" — HGPRT deficiency, hyperuricemia, gout, retardation, self-mutilation.
**Why each option:**
**A.** Autosomal recessive disorders (e.g., PKU) do not show the male predominance and X-linked inheritance pattern seen in Lesch-Nyhan.
**B.** Maternal (mitochondrial) inheritance affects both sexes and presents with neuromuscular and metabolic manifestations (MELAS, LHON), not gout and self-mutilation.
**C.** X-linked dominant disorders affect females more often (e.g., Alport, fragile X has dominant features); Lesch-Nyhan is recessive.
**D.** Correct. The HPRT1 gene is on the X chromosome, so HGPRT deficiency (Lesch-Nyhan syndrome) is X-linked recessive and affects males.