Tangier disease: epidemiology, pathophysiology, and management.

Area of Science:

• Genetics and Molecular Biology
• Lipid Metabolism
• Rare Diseases

Background:

• Tangier disease is a severe inherited disorder characterized by extremely low high-density lipoprotein (HDL) levels.
• It results from mutations in the ATP-binding cassette transporter A1 (ABCA1) gene, crucial for reverse cholesterol transport.
• Affected individuals exhibit cholesteryl ester accumulation in tissues and a deficiency in apolipoprotein A-I (apoA-I).

Purpose of the Study:

• To summarize the key characteristics, genetic basis, and clinical manifestations of Tangier disease.
• To review current understanding of its biochemical and clinical phenotypes.
• To discuss the limitations of existing treatments and explore potential therapeutic strategies.

Main Methods:

• Review of existing literature on Tangier disease.
• Analysis of biochemical and genetic data associated with the condition.
• Evaluation of past and potential future therapeutic interventions.

Main Results:

• Tangier disease presents with plasma HDL < 5 mg/dL, low total cholesterol, and normal/high triglycerides.
• Clinical signs include enlarged tonsils, neuropathy, hepatosplenomegaly, and increased risk of cardiovascular events.
• Mutations in the ABCA1 gene impair cholesterol efflux, a key step in reverse cholesterol transport.

Conclusions:

• There is currently no specific effective treatment for Tangier disease.
• Drugs aimed at increasing HDL levels have proven ineffective in patients.
• Future therapies should focus on selectively increasing mature HDL and restoring cholesterol efflux, potentially through CETP inhibitors or gene therapy.