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

Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease

Francine K Welty  1
Affiliations
Review

Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease

Francine K Welty. Curr Opin Lipidol. 2020 Apr.

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.

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References

    1. Havel RJ, Kane JP. Scriver CR, Beaudet AL, Sly WS, Valle D. Introduction: structure and metabolism of plasma lipoproteins. The metabolic and molecular bases of inherited disease 7th ed.New York, NY: McGraw-Hill; 1995. 1841–1851.
    1. Young SG. Recent progress in understanding apolipoprotein B. Circulation 1990; 82:1574–1594.
    1. Linton MF, Farese RV Jr, Young SG. Familial hypobetalipoproteinemia. J Lipid Res 1993; 34:521–541.
    1. Chen SH, Habib G, Yang CY, et al. Apolipoprotein B-48 is the product of a messenger RNA with an organ-specific in-frame stop codon. Science 1987; 238:363–366.
    1. Berriot-Varoqueaux N, Aggerbeck LP, Samson-Bouma M, et al. The role of the microsomal triglyceride transfer protein in abetalipoproteinemia. Annu Rev Nutr 2000; 20:663–697.