**Question:** Lesh Nyhan syndrome is due to deficiency of:

**Core Concept:** Lesh Nyhan syndrome is a rare autosomal recessive disorder characterized by excessive urination (polyuria), muscle spasms (dystonia), and enlarged liver (hepatosplenomegaly). It is caused by mutations in the DHPR gene, which codes for a protein involved in purine synthesis.

**Why the Correct Answer is Right:** The correct answer, D, is related to purine synthesis, specifically the enzyme hypoxanthine-guanine phosphoribosyl-transerase (HPRT). In Lesh Nyhan syndrome, the deficiency of HPRT leads to increased levels of purine bases (hypoxanthine and guanine) in the body. These elevated purine levels cause excessive urination (polyuria) and muscle spasms (dystonia). The liver enlargement (hepatosplenomegaly) is a consequence of the liver's inability to eliminate the excess purines.

**Why Each Wrong Option is Incorrect:**

A. This option is incorrect as it is not related to purine synthesis or the specific enzyme involved in Lesh Nyhan syndrome.
B. This option is incorrect as it does not address the specific enzyme deficiency and purine synthesis involved in Lesh Nyhan syndrome.
C. This option is incorrect as it is not related to purine synthesis or the specific enzyme involved in Lesh Nyhan syndrome.

**Clinical Pearl:** Lesh Nyhan syndrome is an example of a purine salvage disorder, where the deficiency of HPRT leads to an imbalance in purine salvage pathway, resulting in the clinical features of the syndrome. This is an important concept in understanding the pathogenesis of various inborn errors of purine and pyrimidine biosynthesis and their clinical manifestations.