Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease

Curr Opin Lipidol. 2020 Apr;31(2):49-55. doi: 10.1097/MOL.0000000000000663.


Purpose of review: Several mutations in the apolipoprotein (apo) B, proprotein convertase subtilisin kexin 9 (PCSK9) and microsomal triglyceride transfer protein genes result in low or absent levels of apoB and LDL cholesterol (LDL-C) in plasma which cause familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia (ABL). Mutations in the angiopoietin-like protein 3 ANGPTL3 gene cause familial combined hypolipidemia (FHBL2). Clinical manifestations range from none-to-severe, debilitating and life-threatening disorders. This review summarizes recent genetic, metabolic and clinical findings and management strategies.

Recent findings: Fatty liver, cirrhosis and hepatocellular carcinoma have been reported in FHBL and ABL probably due to decreased triglyceride export from the liver. Loss of function mutations in PCSK-9 and ANGPTL3 cause FHBL but not hepatic steatosis. In 12 case-control studies with 57 973 individuals, an apoB truncation was associated with a 72% reduction in coronary heart disease (odds ratio, 0.28; 95% confidence interval, 0.12-0.64; P = 0.002). PCSK9 inhibitors lowered risk of cardiovascular events in large, randomized trials without apparent adverse sequelae.

Summary: Mutations causing low LDL-C and apoB have provided insight into lipid metabolism, disease associations and the basis for drug development to lower LDL-C in disorders causing high levels of cholesterol. Early diagnosis and treatment is necessary to prevent adverse sequelae from FHBL and ABL.

Publication types

  • Review

MeSH terms

  • Abetalipoproteinemia / blood*
  • Abetalipoproteinemia / genetics
  • Abetalipoproteinemia / metabolism
  • Animals
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism
  • Humans
  • Hypobetalipoproteinemias / blood*
  • Hypobetalipoproteinemias / genetics
  • Hypobetalipoproteinemias / metabolism
  • Lipid Metabolism
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases / blood*
  • Liver Diseases / genetics
  • Liver Diseases / metabolism