Correct Answer: B. Tangier disease
Tangier disease is a rare autosomal recessive disorder of HDL metabolism caused by mutations in the ABCA1 gene, which encodes a cholesterol efflux transporter. The pathognomonic finding is severely depressed HDL cholesterol (often <5 mg/dL) with normal or mildly elevated triglycerides—exactly matching this patient's lipid profile (HDL 5 mg/dL, triglycerides 140 mg/dL). The orange-colored tonsils are pathognomonic and result from massive accumulation of cholesterol esters in macrophages of lymphoid tissue, creating a characteristic lipid-laden appearance. This occurs because ABCA1 dysfunction impairs reverse cholesterol transport, causing cholesterol to accumulate in reticuloendothelial cells. Other clinical features include hepatosplenomegaly, peripheral neuropathy, and premature coronary artery disease. The diagnosis is confirmed by demonstrating severely reduced HDL-C with normal apoB-containing lipoproteins and genetic testing for ABCA1 mutations. The orange discoloration of tonsils is virtually pathognomonic for Tangier disease and distinguishes it from other lipid disorders.
Why the other options are wrong
A. Type I hyperlipoproteinemia — Type I (familial chylomicronemia) presents with severely elevated triglycerides (>1000 mg/dL), not 140 mg/dL, and normal or low HDL. The lipid profile is dominated by chylomicrons, not the selective HDL deficiency seen here. Eruptive xanthomas and lipemic plasma are typical, not orange tonsils. This is an NBE trap pairing 'lipid disorder' with 'abnormal lipids' without discriminating the specific pattern. C. Abetalipoproteinemia — Abetalipoproteinemia is characterized by absent apoB-containing lipoproteins (no LDL, VLDL, chylomicrons) with very low total cholesterol and triglycerides. While HDL is also low, the triglyceride level of 140 mg/dL is too high for abetalipoproteinemia (typically <50 mg/dL). Clinical features include fat malabsorption, steatorrhea, and acanthocytes—not orange tonsils. The lipid pattern is distinctly different from Tangier disease. D. Familial hypercholesterolemia — Familial hypercholesterolemia is characterized by markedly elevated LDL cholesterol and total cholesterol, not the selective HDL deficiency (5 mg/dL) seen here. Triglycerides are typically normal or mildly elevated. Clinical features include tendon xanthomas and corneal arcus, not orange tonsils. The HDL level would be normal or only mildly reduced, making this diagnosis incompatible with the lipid profile.
High-Yield Facts
- Tangier disease: ABCA1 gene mutation → severely reduced HDL-C (<5 mg/dL) with normal/mild triglyceride elevation
- Orange-colored tonsils are pathognomonic for Tangier disease due to cholesterol ester accumulation in macrophages
- Reverse cholesterol transport defect in Tangier disease impairs cholesterol efflux from peripheral tissues to liver
- Premature CAD occurs in Tangier disease despite low LDL, due to HDL deficiency and impaired reverse cholesterol transport
- ABCA1 protein is the rate-limiting step in HDL biogenesis; its absence causes accumulation of cholesterol in reticuloendothelial cells
Mnemonics
TANGIER = Tiny HDL Tiny HDL (<5 mg/dL) | ABCA1 mutation | No reverse cholesterol transport | Golden/orange tonsils | Increased CAD risk | Ester accumulation in macrophages | Reticuloendothelial involvement. Use when you see HDL <5 with orange tonsils. HDL Deficiency Disorders Tangier: Orange tonsils + HDL <5 + normal TG | LCAT deficiency: Fish-eye disease + corneal opacities + HDL <5 | ApoA-I deficiency: Corneal opacities + no tonsil involvement. Tangier is the only one with pathognomonic orange tonsils.
NBE Trap
NBE pairs 'abnormal lipid profile' with 'lipid disorder' to lure students into choosing Type I hyperlipoproteinemia (the most common severe dyslipidemia in exams). The discriminator is the specific HDL value of 5 mg/dL combined with orange tonsils—a pathognomonic triad that only Tangier disease presents.
Clinical Pearl
In Indian clinical practice, Tangier disease is rare but must be suspected when a patient presents with unexplained orange/yellow discoloration of tonsils and lymphoid tissue. The combination of severely depressed HDL with normal triglycerides is the lipid signature that distinguishes it from common dyslipidemia seen in Indian populations (familial hypercholesterolemia, metabolic syndrome). Early recognition prevents unnecessary statin therapy and enables genetic counseling for family screening.
_Reference: Robbins Ch. 5 (Genetic Disorders); Harrison Ch. 356 (Lipid Disorders); KD Tripathi Ch. 30 (Lipid Metabolism)_