Lipid Disorders Flashcards
Defect: Lipoprotein lipase (LPL) deficiency or ApoC-II mutation.
Findings:
↑ Chylomicrons.
↑↑↑ Triglycerides (>1000 mg/dL).
Normal cholesterol.
Clinical Features:
Pancreatitis risk (due to high TGs).
Eruptive xanthomas.
Hepatosplenomegaly.
Creamy supernatant in blood sample.
Treatment: Dietary fat restriction.
Type I - Familial Hyperchylomicronemia
Defect: LDL receptor deficiency or ApoB-100 mutation (autosomal dominant).
Findings:
↑ LDL.
↑↑ Cholesterol.
Normal triglycerides.
Clinical Features:
Premature atherosclerosis (coronary artery disease, MI in 20s-30s).
Tendon xanthomas (Achilles tendon).
Corneal arcus.
Treatment: Statins, PCSK9 inhibitors, ezetimibe.
Type IIa - Familial Hypercholesterolemia
Defect: ApoB-100 overproduction (complex polygenic disorder).
Findings:
↑ LDL and VLDL.
↑↑ Cholesterol.
↑↑ Triglycerides.
Clinical Features:
Metabolic syndrome association (insulin resistance, obesity).
Increased risk for CAD.
Treatment: Statins, fibrates if needed for TGs.
Type IIb - Familial Combined Hyperlipidemia
Defect: ApoE mutation (E2 variant).
Findings:
↑ IDL and Chylomicron remnants.
↑↑ Cholesterol.
↑↑↑ Triglycerides.
Clinical Features:
Palmar xanthomas (yellow discoloration in palmar creases).
Tuberous xanthomas (knees, elbows, buttocks).
Increased risk of atherosclerosis.
Treatment: Statins, fibrates, niacin.
Type III - Familial Dysbetalipoproteinemia
Defect: Increased VLDL production, decreased clearance (polygenic disorder).
Findings:
↑ VLDL.
↑↑ Triglycerides (200-500 mg/dL, can exceed 1000 mg/dL in severe cases).
Normal cholesterol.
Clinical Features:
Increased risk for pancreatitis.
Associated with obesity, diabetes, insulin resistance.
Low HDL.
Treatment: Fibrates (fenofibrate, gemfibrozil), omega-3s, lifestyle modifications.
Type IV - Familial Hypertriglyceridemia
Defect: Increased production and decreased clearance of VLDL and chylomicrons.
Findings:
↑↑ Chylomicrons and VLDL.
↑↑↑ Triglycerides (>1000 mg/dL, severe cases >2000 mg/dL).
Mildly ↑ Cholesterol.
Clinical Features:
Severe pancreatitis risk.
Eruptive xanthomas.
Treatment: Very low-fat diet, fibrates, omega-3s, statins if LDL also high.
Type V - Mixed Hyperlipidemia (Severe Type IV)
Defect: MTP (microsomal triglyceride transfer protein) mutation → No chylomicrons, VLDL, LDL.
Findings:
Low cholesterol, LDL, VLDL.
Fat malabsorption → Steatorrhea.
Clinical Features:
Neurological dysfunction (Vitamin E deficiency → ataxia, neuropathy).
Retinitis pigmentosa (Vitamin A deficiency).
Acanthocytosis (spur cells).
Treatment: Vitamin E and fat-soluble vitamin supplementation.
Abetalipoproteinemia
Defect: ABCA1 mutation (impaired cholesterol efflux to HDL).
Findings:
Extremely low HDL.
Mildly elevated triglycerides.
Clinical Features:
Orange tonsils.
Neuropathy.
Increased CAD risk.
Treatment: None specific, manage cardiovascular risk factors.
Tangier Disease
A 5-year-old boy is brought to the clinic by his parents due to recurrent episodes of abdominal pain. They also note yellowish skin lesions on his trunk and extremities. His past medical history is significant for an episode of acute pancreatitis. Laboratory analysis shows markedly elevated triglycerides (>1000 mg/dL), normal cholesterol, and a creamy supernatant in a blood sample left overnight.
Diagnosis: Familial Hyperchylomicronemia (Type I Dyslipidemia)
Defect: Lipoprotein lipase (LPL) deficiency or ApoC-II deficiency (AR).
Key Features:
Severe hypertriglyceridemia (>1000 mg/dL).
Pancreatitis risk.
Eruptive xanthomas (yellowish papules on skin).
Creamy supernatant in blood sample.
Treatment: Low-fat diet, avoid alcohol, fibrates if needed.
A 32-year-old man presents for evaluation of chest pain with exertion. His father died of a myocardial infarction at age 40. On physical examination, he has tendon xanthomas on his Achilles tendon and corneal arcus. A fasting lipid panel reveals markedly elevated LDL (>300 mg/dL) with normal triglycerides.
Diagnosis: Familial Hypercholesterolemia (Type IIa Dyslipidemia)
Defect: LDL receptor deficiency or ApoB-100 mutation (AD).
Key Features:
Very high LDL levels (>300 mg/dL in heterozygotes, >600 mg/dL in homozygotes).
Early-onset atherosclerosis, CAD, MI.
Tendon xanthomas, corneal arcus.
Treatment: High-intensity statins, PCSK9 inhibitors, ezetimibe.
A 45-year-old man presents with obesity, hypertension, and type 2 diabetes mellitus. His lipid panel shows elevated LDL, VLDL, and triglycerides. His HDL is low. He has a strong family history of premature cardiovascular disease.
Diagnosis: Familial Combined Hyperlipidemia (Type IIb Dyslipidemia)
Defect: ApoB-100 overproduction (Polygenic).
Key Features:
Elevated LDL, VLDL, and triglycerides.
Associated with insulin resistance/metabolic syndrome.
Increased cardiovascular disease risk.
Treatment: Statins, lifestyle modifications (weight loss, exercise), fibrates for triglycerides.
A 55-year-old man presents for a routine checkup. He has yellow plaques on his palms and some large xanthomas over his knees and elbows. His lipid panel shows elevated total cholesterol and triglycerides, with normal LDL. He has a history of peripheral artery disease (PAD) and intermittent leg claudication.
Diagnosis: Familial Dysbetalipoproteinemia (Type III Dyslipidemia)
Defect: ApoE2 mutation (AR; impaired chylomicron/VLDL remnant clearance).
Key Features:
Elevated chylomicrons and IDL remnants.
Palmar xanthomas, tuberous xanthomas.
Peripheral vascular disease, premature CAD.
Treatment: Statins, fibrates, niacin, lifestyle changes.
A 40-year-old woman presents with recurrent episodes of pancreatitis. She is overweight, has a history of gestational diabetes, and drinks alcohol frequently. Her lipid panel shows markedly elevated triglycerides (500-800 mg/dL), normal LDL, and low HDL.
Diagnosis: Familial Hypertriglyceridemia (Type IV Dyslipidemia)
Defect: Increased hepatic VLDL production (Polygenic).
Key Features:
Elevated VLDL, high triglycerides (>500 mg/dL).
Normal LDL, low HDL.
Pancreatitis risk if TGs >1000 mg/dL.
Treatment: Fibrates, omega-3s, statins (if LDL is also elevated).
A 35-year-old man presents with abdominal pain and nausea after consuming alcohol. He has eruptive xanthomas on his back. His lipid panel shows elevated chylomicrons and VLDL, with triglycerides >2000 mg/dL.
Diagnosis: Mixed Hyperlipidemia (Type V Dyslipidemia)
Defect: Increased VLDL and chylomicron production, decreased clearance.
Key Features:
Markedly elevated triglycerides (>2000 mg/dL).
Pancreatitis risk.
Eruptive xanthomas.
Treatment: Fibrates, omega-3s, low-fat diet, avoid alcohol.
A 3-month-old infant presents with failure to thrive, steatorrhea, and difficulty absorbing fat-soluble vitamins. Physical exam reveals ataxia and retinitis pigmentosa. Labs show very low cholesterol, LDL, and VLDL levels. Peripheral smear reveals acanthocytes (spur cells).
Defect: MTP (microsomal triglyceride transfer protein) mutation → No chylomicrons, VLDL, or LDL.
Treatment: Vitamin E supplementation, fat-soluble vitamins (A, D, K, E), low-fat diet.
A 28-year-old man presents with enlarged, orange tonsils and hepatosplenomegaly. His lipid panel reveals extremely low HDL and mild hypertriglyceridemia. His father had a history of premature cardiovascular disease.
Defect: ABCA1 mutation (defective cholesterol efflux to HDL).
Treatment: Manage cardiovascular risk factors.
