The genetic disease familial Hypercholesterolemia that leads to an increase in blood cholesterol is caused
due to
1. consuming cholesterol rich foods
2. mutation in the low-density lipoprotein (LDL) receptor
3. increased hydrolysis of stored intracellular cholesteryl esters
4. increased de novo cholesterol synthesis

Detailed Explanation:

Correct Answer:
2. mutation in the low-density lipoprotein (LDL) receptor

What is Familial Hypercholesterolemia?

Familial hypercholesterolemia (FH) is a genetic disorder that results in high cholesterol levels, particularly high low-density lipoprotein (LDL) cholesterol, which is often referred to as “bad cholesterol.” This condition significantly increases the risk of cardiovascular diseases, including heart attacks and stroke at an early age.

Genetic Cause of FH:

FH is caused by mutations in the LDL receptor gene. The LDL receptor is responsible for binding LDL cholesterol particles from the bloodstream and removing them from circulation. When this receptor is defective or absent due to mutations, the body cannot clear LDL cholesterol efficiently, leading to elevated cholesterol levels in the blood.

This condition can be inherited in an autosomal dominant manner, meaning that even a single copy of the defective gene can cause the disorder. Individuals with heterozygous FH have a 50% reduction in LDL receptor activity, while those with homozygous FH (two copies of the mutated gene) often have even higher cholesterol levels and more severe symptoms.

Why Not the Other Options?

1. Consuming cholesterol-rich foods: While diet plays a role in cholesterol levels, FH is primarily genetic. A diet rich in cholesterol can exacerbate the condition but is not the cause of FH.

2. Increased hydrolysis of stored intracellular cholesteryl esters: This is not directly related to the genetic mutation responsible for FH. The primary issue in FH is the inability of the body to remove LDL from circulation efficiently, rather than excessive cholesterol release from cells.

3. Increased de novo cholesterol synthesis: In FH, cholesterol synthesis is typically normal; the issue lies in the clearance of LDL cholesterol due to defective receptors, not in its production.

Impact of Familial Hypercholesterolemia:

The failure to remove LDL particles from the bloodstream leads to their accumulation, resulting in atherosclerosis (plaque buildup in the arteries). This contributes to cardiovascular diseases such as heart attacks and strokes, often at an early age.