Genetic (Primary) Dyslipidemias

Apo C-II deficiency [a]

Apo C-II (causing functional LPL deficiency)

Recessive

< 1/1 million

Pancreatitis (in some adults), metabolic syndrome (often present)

TG: > 750 mg/dL (> 8.5 mmol/L)

Diet: Severe fat restriction with fat-soluble vitamin supplementation and medium-chain TG supplementation

Cerebrotendinous xanthomatosis [b]

Hepatic mitochondrial 27-hydroxylase defect

Blockage of bile acid synthesis and conversion of cholesterol to cholestanol, which accumulates in blood, nervous system, and other organs

Recessive

Rare

Cataracts, premature CAD, neuropathy, ataxia

Chenodeoxycholic acid

Cholesteryl ester storage disease and Wolman disease [c]

Lysosomal acid lipase deficiency

Recessive

Rare

Premature CAD

Accumulation of cholesteryl esters and TG in lysosomes in the liver, spleen, and lymph nodes

Cirrhosis

Possibly statins

Enzyme replacement

Familial apo AI deficiency/mutations [d]

Apo AI

Unknown

Rare

Corneal opacities, xanthomas, premature CAD (in some people)

HDL: 15–30 mg/dL (0.39–0.78 mmol/L)

Supportive care

Familial chylomicronemic syndrome (formerly LPL deficiency) [e]

LPL gene

APOC2 gene

APOA5 gene

GP1HBP1 gene

LMF1 gene

Recessive

Rare

Hypertriglyceridemia, pancreatitis, eruptive xanthomas, lipemia retinalis

TG > 1000 mg/dL (11.2 mmol/L)

Low-fat diet

Fibrates

Plasma exchange

OlezarsenOlezarsen

Familial combined hyperlipidemia [f]

Unknown, possibly multiple defects and mechanisms

Dominant

1/50 to 1/100

Premature CAD, responsible for approximately 15% of MIs in people < 60 years

Apo B: Disproportionately elevated

TC: 250–500 mg/dL (6.5–13.0 mmol/L)

TG: 250–750 mg/dL (2.8–8.5 mmol/L)

Low-fat diet

Weight loss

Lipid-lowering medications

Familial defective apo B-100 [g]

Apo B (LDL receptor–binding region defect)

Diminished LDL clearance

Dominant

1/700

Xanthomas, arcus corneae, premature CAD

TC: 250–500 mg/dL (6.5–13 mmol/L)

Low-fat diet

Lipid-lowering medications

Familial dysbetalipoproteinemia [h]

Apo E (usually e2/e2 homozygotes)

Diminished chylomicron and VLDL clearance

Recessive (more common) or dominant (less common)

1/5000

Xanthomas (especially tuberous and palmar), yellow palmar creases, premature CAD

TC: 250–500 mg/dL (6.5–13.0 mmol/L)

TG: 250–500 mg/dL (2.8–5.6 mmol/L)

Low-fat diet

Lipid-lowering medications

Familial hypercholesterolemia [i]

LDL receptor defect

Diminished LDL clearance

Codominant

Heterozygotes: 1/200

Tendon xanthomas, arcus corneae, premature CAD (ages 30–50), responsible for approximately 5% of MIs in people < 60 years

TC: 250–500 mg/dL (6.5–13 mmol/L)

Low-fat diet

Lipid-lowering medications

LDL apheresis (for patients who are homozygous and those who are heterozygous with severe disease)

Homozygotes: 1/250,000–1/1 million (increased among French Canadian, Christian Lebanese, and South African populations)

Planar and tendon xanthomas and tuberous xanthomas, premature CAD (before age 18)

TC > 500 mg/dL (> 13 mmol/L)

Low-fat diet

Lipid-lowering medications

LDL apheresis (for patients who are homozygous and those who are heterozygous with severe disease)

Liver transplantation (for homozygous patients)

Familial hypertriglyceridemia [h]

Unknown, possibly multiple defects and mechanisms

Dominant

1/500

Usually no symptoms or findings; occasionally hyperuricemia, sometimes early atherosclerosis

TG: 200–500 mg/dL (2.3–5.6 mmol/L), possibly higher depending on diet and alcohol use

Low-fat diet

Weight loss

Lipid-lowering medications

Familial LCAT deficiency [j]

LCAT gene

Recessive

Extremely rare

Corneal opacities, anemia, chronic kidney disease

HDL: < 10 mg/dL (< 0.26 mmol/L)

Fat restriction

Renal transplantation

Fisheye disease (partial LCAT deficiency)

LCAT gene

Recessive

Extremely rare

Corneal opacities

HDL: < 10 mg/dL (< 0.26 mmol/L)

Supportive care

Hepatic lipase deficiency

Hepatic lipase

Recessive

Extremely rare

Premature CAD

TC: 250–1500 mg/dL (6.5–39 mmol/L)

TG: 395–8200 mg/dL (4.5–93 mmol/L)

HDL: Variable

Low-fat diet, lipid-lowering medications

PCSK9 gain of function mutations

Increased degradation of LDL receptors

Dominant

Unknown

Similar to familial hypercholesterolemia

Low-fat diet

Lipid-lowering medications

Polygenic hypercholesterolemia

Unknown, possibly multiple defects and mechanisms

Variable

Common

Premature CAD

TC: 250–350 mg/dL (6.5–9.0 mmol/L)

Low-fat diet

Lipid-lowering medications

Primary hypoalphalipoproteinemia (familial or nonfamilial)

Unknown, possibly apo A-I, C-III, or A-IV

Dominant

Rare

Premature CAD

HDL: 15–35 mg/dL (0.39–0.91 mmol/L)

Exercise

LDL-lowering medications

Sitosterolemia

ABCG5 and ABCG8 genes

Recessive

Rare

Tendon xanthomas, premature CAD

Fat restriction

Bile acid sequestrants

EzetimibeEzetimibe

Tangier disease

ABCA1 gene

Recessive

Rare

Premature CAD (in some people), peripheral neuropathy, hemolytic anemia, corneal opacities, hepatosplenomegaly, orange tonsils

HDL: < 5 mg/dL (< 0.13 mmol/L)

Low-fat diet