Table 4 Lipoprotein Phenotypes: Clinical findings and impact on management of patients (ref. cited in table [37,38,39])
From: A new phenotypic classification system for dyslipidemias based on the standard lipid panel
Lipoprotein Phenotypes* | Possible Clinical Findings | Dietary and Pharmacological Treatments | Possible Referrals | Additional Lab Tests to consider | Primary Causes ^ | Possible Secondary Causes |
|---|---|---|---|---|---|---|
Type I Chylomicronemia ↑↑↑ TG | - Acute Pancreatitis - Eruptive Xanthomas - Lipemia Retinalis - Mental Status Changes | Very low-fat diet, Fibrates, Fish Oil, Niacin | Nutritionist. Consider Lipidologist for refractory cases. | LPL activity assay. Consider apoC-II mutation testing after excluding secondary causes of TG > 885 mg/dL in pediatric populations [40]. | Familial Hyperchylomicronemia (Autosomal Recessive: LPL, APOC2, GPIHBP1, APOA5, LMF1) | - Type 2 Diabetes - Obesity - Hypothyroidism - Oral Estrogens - Pregnancy - Polycystic Ovarian Syndrome - Alcohol Intake - Chronic Kidney Disease - Non-alcoholic Fatty Liver Disease - Systemic Lupus Erythematosus - Monoclonal Gammopathies - Antiretroviral Therapy - Beta-blockers - Retinoic Acids - Anti-GPIHBP1 antibodies - Lipodystrophy |
Type IIa Hypercholesterolemia ↑↑↑ NonHDL-C | - Xanthelasmas - Tuberous Xanthomas - Tendinous Xanthomas - Corneal Arcus | Statins (first line), Ezetimibe, Bile acid resins, PCSK9 inhibitors | Lipidologist, especially for homozygous FH or statin-refractory cases | Consider genetic testing after excluding secondary causes for LDL-C exceeding: a) 190 mg/dL for age < 20 b) 220 mg/for age 20–29 c) 250 mg/dL for age > 30 [54,55]. | Familial Hypercholesterolemia (Autosomal Dominant: LDLR, APOB, PCSK9) (Autosomal Recessive: LDLRAP1) | - Nephrotic Syndrome - Hypothyroidism - Anabolic Steroids - Cholestatic Liver Disease - Retinoic Acids - Atypical Antipsychotics |
Type IIb Combined hyperlipidemia ↑ TG ↑↑↑ NonHDL-C | No specific signs or symptoms | Statins, Fibrates, Fish Oils, Niacin | Lipidologist for statin-refractory cases | ApoB measurement, Advanced lipid testing (eg: NMR) | Unidentified | - Type 2 Diabetes - Obesity - Nephrotic Syndrome - Cholestatic Liver Disease - Wolman’s disease - Polycystic Ovarian Syndrome - Systemic Lupus Erythematosus - HIV infection - Antiretroviral Therapy - Glucocorticoids - Atypical Antipsychotics - Pregnancy - Retinoic Acids |
Type III Dysbetalipoproteinemia ↑↑ TG↑↑ NonHDL-C | - Palmar xanthomas (pathognomonic) - Tuberous xanthomas - Peripheral Vascular Disease | Statins, Fibrates, Fish Oils, Niacin | Lipidologist for statin-refractory cases | ApoB measurement, ApoE isoform assay, Beta-quantitation, Lipoprotein Electrophoresis | Familial Dysbetalipoproteinemia (Autosomal Recessive of variable penetrance for APOE-e2 variant, but Autosomal Dominant for rare APOE mutations) | - Type 2 Diabetes - Obesity - Alcohol Intake - Hypothyroidism - Glucocorticoids - Chronic Kidney Disease - Menopause - Monoclonal Gammopathies - Systemic Lupus Erythematosus |
Type IVb Hypertriglyceridemia↑↑ TG ↑↑ NonHDL-C | - Insulin resistance - Metabolic Syndrome - Obesity | Statins, Fibrates, Fish Oils, Niacin | Generally none. | ApoB measurement, Advanced lipid testing (eg: NMR) | Unidentified | - Type 2 Diabetes - Obesity - Alcohol Intake - Hypothyroidism - Glucocorticoids - Chronic Kidney Disease - Oral Estrogens |
Type V Mixed hyperlipidemia↑↑↑ TG ↑↑ NonHDL-C | - Acute Pancreatitis - Eruptive Xanthomas - Lipemia Retinalis - Mental Status Changes - Insulin resistance - Metabolic Syndrome - Obesity | Very low-fat diet, Fibrates, Fish Oils, Niacin | Lipidologist and Nutritionist | ApoB measurement, Advanced lipid testing (eg: NMR) | Unidentified | - Type 2 Diabetes - Obesity - Alcohol Intake - Hypothyroidism - Glucocorticoids - Chronic Kidney Disease - Oral Estrogens |
Type VI Hypobetalipoproteinemia↓↓ TG↓↓↓ NonHDL-C | - Steatorrhea - Hepatic steatosis - Failure to thrive - Spinocerebellar Ataxia - Night Blindness - Retinitis Pigmentosa - Bleeding tendency - Acanthocytes | Low-fat diet, Megadose supplementations of Vitamins A and E +/− Vitamin K | Lipidologist, Nutritionist, Ophthalmologist, Neurologist | ApoB measurement, Plasma Vitamin A and E levels, PT/INR | Abetalipoproteinemia (Autosomal Recessive: MTP) Homozygous Hypobetalipoproteinemia (Autosomal Recessive: APOB) | - Chronic Liver Disease - Malnutrition - Fat malabsorption syndromes |