Tangier Disease
🧬 Tangier Disease is a rare inherited lipid disorder characterised by the accumulation of cholesteryl esters throughout the body, particularly within the reticuloendothelial system. It is notable for its striking clinical feature of yellow-orange enlarged tonsils and markedly low HDL levels.
📖 About
- 🧬 Inherited metabolic disorder of cholesterol transport.
- ⬇️ Characterised by extremely low or absent high-density lipoprotein (HDL) and apo A-I.
- First described on Tangier Island, Virginia (1961), giving the condition its name.
🧾 Aetiology & Genetics
- Caused by mutations in the ABCA1 gene, which encodes a membrane transporter responsible for moving cholesterol and phospholipids to apo A-I (essential step in HDL formation).
- Inheritance: Autosomal recessive.
- Pathophysiology: Failure of reverse cholesterol transport → cholesterol ester accumulation in macrophages and tissues → defective HDL metabolism.
🩺 Clinical Features
- 👅 Hyperplastic yellow-orange tonsils – classic and pathognomonic.
- 📉 Low/absent HDL cholesterol → predisposition to atherosclerosis (IHD, PVD, cerebrovascular disease usually manifesting in midlife, ~50s).
- 🫁 Hepatosplenomegaly due to lipid accumulation.
- 🦵 Peripheral neuropathy (can be relapsing-remitting or progressive).
- 🩸 Haematological features: mild thrombocytopenia, reticulocytosis, stomatocytosis, or haemolytic anaemia.
- 👁 Corneal opacities may also occur.
🔬 Investigations
- 🧪 Bloods: Extremely low HDL-cholesterol & apo A-I.
- 📉 FBC: Mild thrombocytopenia, reticulocytosis, stomatocytosis, haemolytic anaemia.
- 🧬 Genetic testing: Biallelic pathogenic variants in ABCA1 confirm diagnosis.
- 🔍 Tissue/lipid studies may show foam cell infiltration in bone marrow or lymph nodes.
💊 Management
- 🎭 Supportive and symptomatic only – no curative therapy.
- 👅 Tonsillectomy if tonsillar hypertrophy causes airway or swallowing problems.
- 🦵 Ankle-foot orthosis for disabling peripheral neuropathy.
- 👁 Corneal transplantation for severe corneal opacities.
- 🫀 Manage cardiovascular risk aggressively (statins, lifestyle modification, control of diabetes and hypertension).
- 🩸 Supportive care for cytopenias (e.g. transfusion in severe haemolytic anaemia).
📚 Key OSCE / Exam Pearls
- 🧡 Orange tonsils + low HDL is highly suggestive of Tangier Disease.
- Think of Tangier when you see neuropathy + hepatosplenomegaly + premature atherosclerosis.
- Pathology revolves around impaired reverse cholesterol transport.
- Management is supportive – no definitive cure yet.
📖 References
