title: Hypobetalipoproteinemia and abetalipoproteinemia.
abstract: OBJECTIVE
  Several mutations in the apoB, proprotein convertase subtilisin/kexin type 9 (PCSK9), and MTP genes result in low or absent levels of apoB and LDL-cholesterol in plasma, which cause familial hypobetalipoproteinemia and abetalipoproteinemia. Mutations in the ANGPTL3 gene cause familial combined hypolipidemia. Clinical manifestations range from none to severe, debilitating, and life-threatening disorders. This review summarizes recent genetic, metabolic, and clinical findings and presents an update on management strategies.
  
  
  RESULTS
  Cases of cirrhosis and hepatocellular carcinoma have now been identified in heterozygous familial hypobetalipoproteinemia probably because of decreased triglyceride transport capacity from the liver. ANGPTL3 mutations cause low levels of LDL-cholesterol and low HDL-cholesterol in compound heterozygotes and homozygous individuals, decrease reverse cholesterol transport, and lower glucose levels. The effect on atherosclerosis is unknown; however, severe fatty liver has been identified. Loss-of-function mutations in PCSK9 cause familial hypobetalipoproteinemia, which appears to lower risk for coronary artery disease and has no adverse sequelae. Phase III clinical trials are now underway examining the effect of PCSK9 inhibitors on cardiovascular events in combination with statin drugs.
  
  
  CONCLUSIONS
  Mutations causing low LDL-cholesterol and apoB have provided insight into lipid metabolism, disease associations, and the basis for drug development to lower LDL-cholesterol in disorders causing high levels of cholesterol. Early diagnosis and treatment are necessary to prevent adverse sequelae from familial hypobetalipoproteinemia and abetalipoproteinemia.
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Francine K
authors.initials: FK
authors.lastname: Welty
mesh_terms: D000012:Abetalipoproteinemia / Q000097:blood / Q000235:genetics; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics; D001693:Biological Transport, Active / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics; D006801:Humans; D052476:Hypobetalipoproteinemia, Familial, Apolipoprotein B / Q000097:blood / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics*; D008103:Liver Cirrhosis / Q000097:blood / Q000235:genetics; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics; D009154:Mutation; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood / Q000235:genetics
chemical_list: C479896:ANGPTL3 protein, human; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D014280:Triglycerides; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
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