genetic lipoprotein disorders

Last reviewed 09/2021

Features of Major Genetic Lipoprotein Disorders


Principle plasma abnormality

[corresponding Fredrickson classification**]

Clinical FeaturesEstimated Frequency

Heterozygous familial hypercholesterolemia


+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 hypercholesterolemiasame frequency as heterozygous familial hypercholesterolemia

Familial combined hyperlipidemia


  • 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


+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


(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


* CAD = coronary artery disease; HDL-C = high-density lipoprotein cholesterol; IDL = intermediate-density lipoproteins; LDL = low-density lipoproteins; MI = myocardial infarction; TC = total cholesterol; TG = triglycerides; VLDL = very low-density lipoproteins ** See Fredrickson Classification of Lipid Disorders More information.

The lipid levels in the table are a guide to the patterns of found in the dyslipidaemias. Diagnosis is made by taking into account other factors such as age, sex, ethnic origin, family history and physical findings and other laboratory tests such as apolipoproteins.

NB: 1mmol/cholesterol = 39mg/dl; 1 mmol triglyceride = 89mg/dl