**Question:** Lesch-Nyhan syndrome is caused by the deficiency of which enzyme?

**Core Concept:** Lesch-Nyhan syndrome is a rare genetic disorder characterized by excessive uric acid production and its accumulation in the body, leading to various neurological and behavioral symptoms. This disorder is caused by a deficiency in a specific enzyme.

**Why the Correct Answer is Right:** Lesch-Nyhan syndrome results from a deficiency in the enzyme hypoxanthine-guanine phosphoribosyl-transerase (HPRT), which is essential for purine nucleotide synthesis. When HPRT is lacking, uric acid accumulates, causing neurological and behavioral symptoms.

**Why Each Wrong Option is Incorrect:**

A. Hypoxanthine-guanine phosphoribosyl-transerase (HPRT) deficiency is responsible for Lesch-Nyhan syndrome, not the absence of uricase (uric acid-degrading enzyme).

B. Although high uric acid levels contribute to Lesch-Nyhan syndrome, the deficiency responsible is in HPRT, not adenosine deaminase (ADA) which is involved in purine degradation.

C. Lesch-Nyhan syndrome is caused by a deficiency in hypoxanthine-guanine phosphoribosyl-transerase (HPRT), not phosphoribosyl pyrophosphate synthetase (PPPYS), which is involved in purine synthesis.

D. Hypoxanthine-guanine phosphoribosyl-transerase (HPRT) deficiency is responsible for Lesch-Nyhan syndrome, not phosphoribosyl pyrophosphate synthetase (PRPS), which is involved in purine synthesis.

**Clinical Pearl:**

Understanding the role of HPRT in purine synthesis is essential for grasping the pathogenesis of Lesch-Nyhan syndrome. HPRT is crucial for purine nucleotide synthesis, and its deficiency leads to excessive uric acid accumulation, which results in neurological and behavioral symptoms. This emphasizes the importance of maintaining an appropriate balance of purine and pyrimidine nucleotides in the body.

**Correct Answer:** D. Hypoxanthine-guanine phosphoribosyl-transerase (HPRT) deficiency

**Why Each Wrong Option is Incorrect:**

A, B, C, and E all involve enzymes involved in purine degradation (ADP-ribose pyrophosphatase, adenosine deaminase, phosphoribosyl pyrophosphate synthetase, and phosphoribosyl pyrophosphatase) which are not directly related to purine synthesis.

**Clinical Pearl:**

Recognizing the correct enzyme involved in purine synthesis (HPRT) helps in understanding the pathogenesis of Lesch-Nyhan syndrome. The deficiency of HPRT leads to an imbalance in purine and pyrimidine nucleotide synthesis, causing the accumulation of uric acid and resulting in neurological and behavioral symptoms.