Disorder of cholesterol transport

Disorders of cholesterol transport can lead to various health issues, primarily affecting lipid metabolism and increasing the risk of cardiovascular diseases. One of the most notable conditions related to disrupted cholesterol transport is familial hypercholesterolemia (FH), which is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) due to genetic mutations that impair the body's ability to remove LDL from the bloodstream.

Key Disorders Related to Cholesterol Transport

1. Familial Hypercholesterolemia (FH):

   • Cause: Mutations in the LDL receptor gene, leading to reduced clearance of LDL cholesterol from the blood.
   • Symptoms: Elevated LDL cholesterol levels, premature coronary artery disease, and familial history of early heart disease.

2. Sitosterolemia:

   • Cause: Genetic mutations affecting sterol transport (e.g., ABCG5 and ABCG8), leading to the accumulation of plant sterols in the body.
   • Symptoms: Cholesterol levels may be normal, but elevated plant sterols can lead to xanthomas and atherosclerosis.

3. Cholesterol Ester Storage Disease:

   • Cause: Deficiencies in enzymes involved in cholesterol esterification (ACAT1), leading to intracellular accumulation of cholesterol esters.
   • Symptoms: Often presents with hepatosplenomegaly, growth retardation, and risk of cardiovascular disease.

4. Tangier Disease:

   • Cause: Mutations in the ATP-binding cassette transporter ABCA1, leading to a very low level of high-density lipoprotein (HDL) cholesterol.
   • Symptoms: Severe HDL deficiency, orange tonsils, peripheral neuropathy, and increased risk of coronary artery disease.

5. Niemann-Pick Type C Disease:

   • Cause: Mutations affecting cholesterol transport within cells, leading to accumulation in lysosomes.
   • Symptoms: Neurological symptoms, hepatosplenomegaly, and progressive dementia.

Mechanisms of Disorder

• Overproduction of Cholesterol: In some conditions, the liver may produce excess cholesterol, contributing to elevated serum cholesterol levels.
• Decreased Clearance: Issues with the receptors responsible for removing LDL cholesterol from circulation can lead to increased plasma cholesterol levels.
• Impaired Transport Proteins: The function of transport proteins can be disrupted due to genetic mutations or other factors, affecting how cholesterol is mobilized and utilized in the body.

Conclusion

Disorders of cholesterol transport are critical due to their implications for cardiovascular health and overall metabolism. Early diagnosis, genetic counseling, and targeted therapies can help manage these conditions and reduce associated risks. Lifestyle interventions, including dietary modifications and regular exercise, are also essential in managing cholesterol levels for individuals with these disorders.