Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease.

Abstract

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.

• Authors: Francine K Welty
• Journal: Current opinion in lipidology (Curr Opin Lipidol) Vol. 31 Issue 2 Pg. 49-55 (04 2020) ISSN: 1473-6535 [Electronic] England
• PMID: 32039990 (Publication Type: Journal Article, Review)

Topics

• Abetalipoproteinemia (blood, genetics, metabolism)
• Animals
• Cardiovascular Diseases (blood, genetics, metabolism)
• Humans
• Hypobetalipoproteinemias (blood, genetics, metabolism)
• Lipid Metabolism
• Liver (metabolism, pathology)
• Liver Diseases (blood, genetics, metabolism)