Lipoprotein lipase deficiency
🩸 In Familial Lipoprotein Lipase Deficiency, the blood can appear milky (lipemic plasma) due to high chylomicron levels. This rare condition is also called Familial Chylomicronemia Syndrome.
📖 About
- A rare inherited lipid disorder caused by absent or defective lipoprotein lipase (LPL), the key enzyme responsible for hydrolysing triglycerides in circulating chylomicrons and VLDL.
- LPL is produced mainly in adipose tissue, skeletal muscle, and myocardium.
- Without functioning LPL, triglycerides accumulate, leading to severe hypertriglyceridemia and risk of acute pancreatitis.
- Incidence: ~1 in 1,000,000 (rare) but more common in certain populations (e.g., French-Canadian, Mennonite, and some Middle Eastern groups).
🧬 Aetiology
- Inheritance: Autosomal recessive.
- Genetic cause: Mutations in the LPL gene (chromosome 8p22).
- Variants in co-factors such as APOC2, APOA5, GPIHBP1, or LMF1 can also produce similar phenotypes.
🩺 Clinical Features
- Symptoms often start in childhood, sometimes after fatty meals.
- 🌟 Pancreatitis: Recurrent attacks are the most serious complication.
- 🧴 Eruptive xanthomas: Yellow papules on the trunk, buttocks, knees, and arms.
- 👁 Lipaemia retinalis: Milky-white retinal vessels due to very high triglycerides.
- 📏 Hepatosplenomegaly: Fat deposition in liver and spleen.
- 📉 Often not strongly associated with premature atherosclerotic cardiovascular disease (unlike familial hypercholesterolemia).
🔎 Differentials
- Familial combined hyperlipidemia (common, less severe TG elevation).
- Secondary hypertriglyceridemia from uncontrolled diabetes, hypothyroidism, obesity, renal failure.
- Drug-induced: corticosteroids, estrogens, retinoids, protease inhibitors.
🧪 Investigations
- 💉 Fasting triglycerides: Often >10 mmol/L (880 mg/dL), can exceed 50 mmol/L in acute settings.
- 🧪 Visual test: Plasma appears milky and may form a creamy supernatant layer after standing.
- 📊 Lipoprotein electrophoresis/ultracentrifugation: Confirms excess chylomicrons.
- 🧬 Genetic testing: Confirms mutations in LPL or related genes.
⚕️ Management
- 🍽️ Very low-fat diet: Strict restriction of long-chain triglycerides (<10–15% of total calories).
- 🥥 Medium-chain triglycerides (MCTs): Absorbed directly into the portal system, bypassing LPL.
- 🚫 Avoid alcohol: Strong trigger for hypertriglyceridemia and pancreatitis.
- 💊 Drug therapy: Fibrates, omega-3 fatty acids, and niacin usually ineffective in true LPL deficiency (since they act by upregulating LPL activity).
- 🧬 Novel therapies: Gene therapy with alipogene tiparvovec (Glybera) was approved in Europe but later withdrawn due to cost; research continues into ApoC3 inhibitors and ANGPTL3 inhibitors.
- 👨👩👧 Genetic counselling for families.
💡 Exam Pearls
- 💉 Milky plasma after refrigeration = pathognomonic clue.
- 🧴 Eruptive xanthomas appear with TG >11 mmol/L.
- 🚑 Main risk = acute pancreatitis, not premature atherosclerosis.
- 🧬 Inheritance = autosomal recessive (contrast with familial hypercholesterolemia which is autosomal dominant).
📚 References
- NHS – Familial lipid disorders
- Brunzell JD. Familial lipoprotein lipase deficiency and other causes of the chylomicronemia syndrome. In: Endotext [Internet]. 2019.
- European Atherosclerosis Society Consensus Panel. Eur Heart J. 2020;41(1):99–109.
