Primary Hyperlipoproteinemias Caused by Known Single-Gene Mutations
| Genetic Disorder | Protein (Gene) Defect | Lipoproteins Elevated | Clinical Findings | Genetic Transmission | Estimated Incidence |
|---|---|---|---|---|---|
| Hypertriglyceridemia | |||||
| Lipoprotein lipase deficiency | LPL (LPL) | Chylomicrons, VLDL | Eruptive xanthomas, hepatosplenomegaly, pancreatitis | AR | ~1/1,000,000 |
| Familial apo CII deficiency | Apo CII (APOC2) | Chylomicrons, VLDL | Eruptive xanthomas, hepatosplenomegaly, pancreatitis | AR | <1/1,000,000 |
| Apo A-V deficiency | Apo A-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 |
| Hypercholesterolemia | |||||
| 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 |
Abbreviations: AD, autosomal dominant; apo, apolipoprotein; AR, autosomal recessive; ARH, autosomal recessive hypercholesterolemia; CHD, coronary heart disease; LDL, low-density lipoprotein; LPL, lipoprotein lipase; PVD, peripheral vascular disease; VLDL, very-low density lipoprotein.