A child has strikingly enlarged, yellow-orange tonsils. A fasting lipid panel shows HDL cholesterol near zero and a markedly reduced apolipoprotein A-I. He also has mild hepatosplenomegaly and patchy sensory loss consistent with peripheral neuropathy.
AR; ABCA1 (ATP-binding cassette transporter A1)
ABCA1 is the pump that exports free cholesterol and phospholipids out of cells onto lipid-poor apolipoprotein A-I, the first step in building nascent HDL. Without a working pump:
- ApoA-I reaches the cell surface but has nothing to load onto, so it is degraded within hours instead of maturing into HDL. HDL-C and apoA-I both fall toward zero.
- The cholesterol that should have left the cell stays inside, and macrophages throughout the reticuloendothelial system (tonsils, spleen, liver, bone marrow, peripheral nerves, cornea) swell with cholesteryl esters.
- The familial hypercholesterolemia intuition, low HDL means high cardiovascular risk, only partly applies here: LDL is also low in Tangier disease, so atherosclerosis is accelerated but more modest than the HDL number alone would predict.
- Hyperplastic, yellow-orange tonsils (the classic finding)
- HDL-C near zero, apoA-I markedly reduced
- Hepatosplenomegaly
- Peripheral neuropathy (relapsing-remitting or chronic progressive)
- Corneal opacities, usually without visual impairment
- Premature coronary artery disease, typically 6th-7th decade
- Fasting lipid panel: HDL-C near zero, low apoA-I, mild hypertriglyceridemia
- Confirm with biallelic pathogenic ABCA1 variants
- Enlarged orange tonsils plus near-absent HDL is close to pathognomonic; don't mistake the tonsil finding for chronic tonsillitis
- Supportive; no therapy restores ABCA1 function
- Standard cardiovascular risk-factor management
- Monitor for progression of peripheral neuropathy
"Tangier = tangerine tonsils" 🍊: hyperplastic, yellow-orange tonsils are the most recognizable finding, the color comes from cholesteryl-ester-engorged macrophages packed into the tonsil, not a pigment problem.
"No efflux, no HDL": ABCA1 is the efflux pump that loads cholesterol onto apoA-I to build HDL. No pump means apoA-I is degraded before HDL ever forms (HDL crashes to near zero) while the cholesterol it should have carried away backs up inside macrophages, the same lipid-laden macrophages that turn the tonsils orange.