Hyperlipoproteinemia is characterized by hypercholesterolemia, isolated hypertriglyceridemia, or both. Genetic causes of hyperlipoproteinemia are summarized in Table 181-1. Diabetes mellitus, obesity, ethanol consumption, oral contraceptives, glucocorticoids, renal disease, hepatic disease, and hypothyroidism can cause secondary hyperlipoproteinemias or worsen underlying hyperlipoproteinemic states.
TABLE 181-1Primary Hyperlipoproteinemias Caused by Known Single-Gene Mutations ||Download (.pdf) TABLE 181-1 Primary Hyperlipoproteinemias Caused by Known Single-Gene Mutations
|GENETIC DISORDER ||PROTEIN (GENE) DEFECT ||LIPOPROTEINS ELEVATED ||CLINICAL FINDINGS ||GENETIC TRANSMISSION ||ESTIMATED INCIDENCE |
|Lipoprotein lipase deficiency ||LPL (LPL) ||Chylomicrons, VLDL ||Eruptive xanthomas, hepatosplenomegaly, pancreatitis ||AR ||∼1/1,000,000 |
|Familial apoC-II deficiency ||ApoC-II (APOC2) ||Chylomicrons, VLDL ||Eruptive xanthomas, hepatosplenomegaly, pancreatitis ||AR ||<1/1,000,000 |
|ApoA-V deficiency ||ApoA-V (APOA5) ||Chylomicrons, VLDL ||Eruptive xanthomas, hepatosplenomegaly, pancreatitis ||AR ||<1/1,000,000 |
|GPIHBP1 deficiency ||GPIHBP1 ||Chylomicrons ||Eruptive xanthomas, pancreatitis ||AR ||<1/1,000,000 |
|Combined hyperlipidemia |
|Familial hepatic lipase deficiency ||Hepatic lipase (LIPC) ||VLDL remnants, HDL ||Pancreatitis, CHD ||AR ||<1/1,000,000 |
|Familial dysbetalipoproteinemia ||ApoE (APOE) ||Chylomicron remnants, VLDL remnants ||Palmar and tuberoeruptive xanthomas, CHD, PVD ||AR ||∼1/10,000 |
|Familial hypercholesterolemia ||LDL receptor (LDLR) ||LDL ||Tendon xanthomas, CHD ||AD ||∼1/250 to 1/500 |
|Familial defective apoB-100 ||ApoB-100 (APOB) ||LDL ||Tendon xanthomas, CHD ||AD ||<∼1/1500 |
|Autosomal dominant hypercholesterolemia, type 3 ||PCSK9 (PCSK9) ||LDL ||Tendon xanthomas, CHD ||AD ||<1/1,000,000 |
|Autosomal recessive hypercholesterolemia ||ARH (LDLRAP) ||LDL ||Tendon xanthomas, CHD ||AR ||<1/1,000,000 |
|Sitosterolemia ||ABCG5 or ABCG8 ||LDL ||Tendon xanthomas, CHD ||AR ||<1/1,000,000 |
Standard lipoprotein analysis assesses total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Both LDL and HDL cholesterol levels are temporarily decreased for several weeks after myocardial infarction or acute inflammatory states, but can be accurately measured if blood is obtained within 8 h of the event.
Elevated levels of fasting plasma total cholesterol (>5.2 mmol/L [>200 mg/dL]) in the presence of normal levels of triglycerides are almost always associated with increased concentrations of plasma LDL cholesterol. Elevations of LDL cholesterol can result from single-gene defects, from polygenic disorders, or from the secondary effects of other disease states.
FAMILIAL HYPERCHOLESTEROLEMIA (FH)
FH is a codominant genetic disorder caused by mutations in the gene for the LDL receptor. Plasma LDL levels are elevated at birth and remain so throughout life. In untreated heterozygous adults, total cholesterol levels range from 7.1 to 12.9 mmol/L (275–500 mg/dL). Plasma triglyceride levels are typically normal, and HDL cholesterol levels are normal or reduced. Heterozygotes are prone to accelerated atherosclerosis and premature coronary artery disease (CAD). Tendon xanthomas (most commonly of the Achilles tendons and the extensor tendons of the knuckles), tuberous xanthomas (softer, painless nodules on the ankles and buttocks), and xanthelasmas (deposits ...