Hypobetalipoproteinemia and Abetalipoproteinemia #MMPMID24751931
Welty FK
Curr Opin Lipidol 2014[Jun]; 25 (3): 161-8 PMID24751931show ga
Purpose of Review: Several mutations in the apoB, PCSK9 and MTP genes result in low or absent levels of apoB and LDL-C in plasma which cause familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia (ABL). 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. Recent findings: Cases of cirrhosis and hepatocellular carcinoma have now been identified in heterozygous FHBL probably due to decreased triglyceride transport capacity from the liver. ANGPTL3 mutations cause low levels of LDL-C and low HDL-C in compound heterozygotes and homozygous subjects, 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 PCSK-9 cause FHBL which appears to lower risk for CAD and have no adverse sequelae. Phase III clinical trials are now underway examining the effect of PCSK-9 inhibitors on cardiovascular events in combination with statin drugs. 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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Curr+Opin+Lipidol 2014 ; 25 (3): 161-8
