Problem 12 - Clinical Chemistry

Question

Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase results in which disease? a. Allantoinism b. Glycogen storage disease c. Lesch-Nyhan syndrome d. Megaloblastic anemia

Step-by-Step Solution

Answer

c. Lesch-Nyhan syndrome

Step 1 - Understand the Enzyme Involved

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is an enzyme that plays a crucial role in the purine salvage pathway. This pathway is important for recycling purines from degraded DNA back into useful nucleotides.

Step 2 - Analyze Each Disease Option

Evaluate which disease is specifically linked to a deficiency in HGPRT: a. Allantoinism is not related to HGPRT deficiency. b. Glycogen storage disease involves errors in glycogen metabolism, which are not related to HGPRT. c. Lesch-Nyhan syndrome is directly caused by a deficiency in HGPRT. d. Megaloblastic anemia is related to deficiencies in vitamin B12 or folate, not HGPRT.

Step 3 - Identify the Correct Answer

From the analysis, it is clear that Lesch-Nyhan syndrome is the disease caused by a complete deficiency of HGPRT.

Key Concepts

hypoxanthine-guanine phosphoribosyltransferase

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is an essential enzyme in the body. It helps recycle purines, which are crucial building blocks of DNA and RNA. When DNA breaks down, purines like hypoxanthine and guanine are released. Instead of wasting these important molecules, the purine salvage pathway, with the help of HGPRT, converts them back into useful nucleotides. Without HGPRT, this recycling process cannot happen, leading to a buildup of purine waste products. This enzyme's absence or malfunction plays a critical role in several metabolic conditions, including Lesch-Nyhan syndrome.

purine salvage pathway

The purine salvage pathway is a vital metabolic process. It recycles purines from degraded DNA and RNA back into nucleotides. Here’s how it generally works: when DNA breaks down, it releases purines like hypoxanthine and guanine. Instead of discarding these valuable materials, the body reuses them. This recycling ensures a steady supply of purines for DNA and RNA synthesis, reducing the need to make them from scratch, which saves energy. HGPRT plays a key role in this pathway. It attaches these recycled purines to ribose-phosphate, forming new nucleotides. If HGPRT is missing or deficient, as in Lesch-Nyhan syndrome, purine recycling is significantly impaired, leading to various health problems.

enzyme deficiency

Enzyme deficiencies can lead to serious medical conditions. An enzyme's role is to accelerate chemical reactions in the body. When an enzyme is missing or not working right, these reactions either slow down or don’t happen at all, causing a buildup of substrates and a shortage of products. In the case of HGPRT deficiency, the lack of this enzyme disrupts the purine salvage pathway. This leads to high levels of uric acid, a waste product of purine metabolism. Over time, uric acid can form crystals in the joints, cause kidney stones, and affect the nervous system. Complete deficiency of HGPRT specifically results in Lesch-Nyhan syndrome, which is characterized by severe neurological and behavioral abnormalities and overproduction of uric acid.