Question

A patient with orange-colored tonsils has a triglyceride level of 140 mg/dL and very low HDL cholesterol, 5 mg/dL. What is the most probable diagnosis?

• A. Familial hypercholesterolemia
• B. Tangier disease
• C. Type I hyperlipoproteinemia
• D. Abetalipoproteinemia

Hint:

Orange tonsils with very low HDL is a classic clue for Tangier disease.

Answer 1

The Correct Option is B

Step 1: Understanding the Question:
The presence of "orange tonsils" combined with profoundly low levels of High-Density Lipoprotein (HDL) cholesterol (hypoalphalipoproteinemia) is a pathognomonic clinical presentation.
This suggests a severe defect in the reverse cholesterol transport system, specifically Tangier disease.
Step 2: Detailed Explanation:

The Molecular Defect: Tangier disease is a rare autosomal recessive disorder caused by a mutation in the ABCA1 gene.

Function of ABCA1: The ABCA1 (ATP-binding cassette transporter A1) protein is responsible for pumping cholesterol out of cells and onto lipid-poor ApoA-I to initiate the formation of nascent HDL particles.

Biochemical Consequences:

Without functional ABCA1, cells cannot export excess cholesterol to the bloodstream.

This results in extremely low plasma HDL-C levels, typically less than 5 mg/dL.

The trapped cholesterol is stored as cholesterol esters within macrophages of the reticuloendothelial system.


Clinical Manifestations:

Orange-colored Tonsils: This is the hallmark of the disease. The tonsils enlarge and turn orange because of the massive accumulation of yellowish-orange cholesterol esters in the tonsillar macrophages.

Hepatosplenomegaly: Due to lipid accumulation in the liver and spleen.

Peripheral Neuropathy: Often occurs due to lipid deposition within nerve sheaths.

Corneal Opacities: May be observed in some patients.


Comparison with other lipid disorders:

Abetalipoproteinemia: Characterized by very low LDL and VLDL; presents with fat malabsorption and acanthocytes.

Type I Hyperlipoproteinemia: Presents with severe hypertriglyceridemia and pancreatitis.


Step 3: Final Answer:
Tangier disease is the correct diagnosis, identified by the unique accumulation of cholesterol in the tonsils and nearly absent HDL cholesterol.