Genetic lipoprotein disorders

Disorder

Principle plasma abnormality

[corresponding Fredrickson classification**]

Clinical Features

Estimated Frequency

Heterozygous familial hypercholesterolemia

TC>7.5,LDL>5.0,TG<2.3

+LDL only (inherited abnormality of the LDL receptor) [IIa]

• tendinous xanthomas
• corneal arcus
• premature CAD
• family history of hypercholesterolemia

• 0.2% of general population
• 5% of MI survivors <60 yr old
• Autosomal codominant

Familial defective apolipoprotein B

+LDL (inherited abnormality of apoprotein B interferes with binding to LDL receptor) [IIa]

same clinical features as heterozygous familial hypercholesterolemia

same frequency as heterozygous familial hypercholesterolemia

Familial combined hyperlipidemia

TC>7.0,LDL>4.0,HDL<1.0,TG>3.5

• 1/3: LDL only [IIa]
• 1/3: VLDL only [IV]
• 1/3: LDL and VLDL [IIb]

Apo-B overproduction is common

• usually >30 yr old
• often overweight
• usually no xanthomas
• premature CAD
• different generations have different lipoprotein abnormalities

• 0.5% of general population
• 15% of MI survivors <60 yr old
• autosomal dominant

Polygenic hypercholesterolemia

TC>6.5,LDL>4.0,TG<2.3

+LDL [IIa]

• premature CAD
• no xanthomas
• possible family history of hypercholesterolemia

• unknown

Familial hypertriglyceridemia (2.3-10 mmol/L)

+VLDL only (high VLDL production, decreased lipoprotein lipase activity) [IV]

• often overweight
• >30 yr old
• often diabetic
• hyperuriaemic
• may or may not have premature CAD
• determined by family history and HDL-C

• 1% of general population
• 5% of MI survivors <60 yr old
• autosomal dominant

Severe hypertriglyceridemia ( TG >10 mmol/L))

+Chylomicrons and VLDL (high VLDL production, decreased lipoprotein lipase activity) [V]

• usually middle-aged
• often obese
• often hyperuricaemic
• usually diabetic
• risk for recurrent pancreatitis

• unknown

Familial hypoalpha- lipoproteinemia

reduced HDL (< 0.78 mmol/L) in males; <0.90 mmol/L) in females)

(decreased apo A-1 production)

• premature CAD

• 1% of general population
• 25-30% of patients with premature CAD
• autosomal recessive

Dysbetalipoproteinemia

(TC 9-14 mmol/L; TG 9-14 mmol/L)

+IDL, +chylomicron remnants

(defective apo E2/2) [III]

• yellow palmar creases
• palmar xanthomas
• tuberoeruptive xanthomas
• premature CAD

• uncommon 3% of MI survivors
• autosomal recessive