Makindo Medical Notes

🧬 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

• Tangier Disease – PubMed Review
• OMIM Entry: Tangier Disease
• Orphanet: Tangier Disease