Tangier disease

Tangier disease is a rare inherited disorder caused by pathogenic variants in ABCA1 that impair cellular cholesterol export. It causes extremely low HDL cholesterol and may produce orange tonsils, neuropathy, and enlarged organs.

ABCA1: ABCA1 is a membrane transporter that moves cellular cholesterol and phospholipids onto apolipoprotein A-I. Variants in this transporter cause Tangier disease by disrupting cholesterol export.
Orange tonsils: Orange tonsils are enlarged tonsils with yellow-orange discoloration caused by lipid-laden cells. They are a distinctive physical finding in Tangier disease.
Autosomal recessive inheritance: Autosomal recessive inheritance occurs when a condition results from pathogenic variants in both copies of an autosomal gene. Tangier disease typically requires disease-causing ABCA1 variants on both gene copies.
Lipid panel: A lipid panel is a blood test measuring cholesterol fractions and triglycerides. Near-absent HDL cholesterol is a major clue prompting evaluation for Tangier disease.
Apolipoprotein A-I: Apolipoprotein A-I is the main protein component of high-density lipoprotein and an acceptor of cellular cholesterol. ABCA1 normally transfers cholesterol to this protein to begin HDL formation.
Peripheral neuropathy: Peripheral neuropathy is damage to nerves outside the brain and spinal cord. Tangier disease can cause sensory loss, weakness, or other nerve symptoms.
Lipoprotein: A lipoprotein is a particle that carries water-insoluble fats through blood and other bodily fluids. HDL is one class of lipoprotein whose formation is impaired in this disorder.
Genetic testing: Genetic testing analyzes DNA to identify variants associated with inherited conditions. Testing ABCA1 can confirm the molecular diagnosis and support family counseling.
Cholesterol efflux: Cholesterol efflux is the movement of cholesterol from cells to extracellular acceptors. Impaired efflux is the cellular defect underlying Tangier disease.
Hepatosplenomegaly: Hepatosplenomegaly is enlargement of both the liver and spleen. Lipid accumulation can enlarge these organs in affected people.

Linked from 1 page

AbetalipoproteinemiaCompared with: Both conditions can cause neuropathy, but Tangier disease affects HDL metabolism rather than apoB particle assembly.