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Context:Familial hypobetalipoproteinemia (FHBL) is a codominant disorder of lipoprotein metabolism characterized by decreased plasma concentrations of low-density lipoprotein (LDL)-cholesterol and apolipoprotein B (apoB).Objective:The objective was to examine the effect of heterozygous APOB L343V FHBL on postprandial triglyceride-rich lipoprotein (TRL) and fasting lipoprotein metabolism.Methods:Plasma incremental area under the curve apoB-48 and apoB-48 kinetics were determined after ingestion of a standardized oral fat load using compartmental modeling. Very low-density lipoprotein (VLDL)-, intermediate-density lipoprotein (IDL)-, and LDL-apoB kinetics were determined in the fasting state using stable isotope methods and compartmental modeling.Results:The postprandial incremental area under the curve (0–10 h) in FHBL subjects (n = 3) was lower for large TRL-triglyceride (−77%; P < .0001), small TRL-cholesterol (−83%; P < .001), small TRL-triglyceride (−88%; P < .001), and for plasma triglyceride (−70%; P < .01) and apoB (−63%; P < .0001) compared with controls. Compartmental analysis showed that apoB-48 production was lower (−91%; P < .05) compared with controls. VLDL-apoB concentrations in FHBL subjects (n = 2) were lower by more than 75% compared with healthy, normolipidemic control subjects (P < .01). The VLDL-apoB fractional catabolic rate (FCR) was more than 5-fold higher in the FHBL subjects (P = .07). ApoB production rates and IDL- and LDL-apoB FCRs were not different between FHBL subjects and controls.Conclusions:We conclude that when compared to controls, APOB L343V FHBL heterozygotes show lower TRL production with normal postprandial TRL particle clearance. In contrast, VLDL-apoB production was normal, whereas the FCR was higher in heterozygotes compared with lean control subjects. These mechanisms account for the marked hypolipidemic state observed in these FHBL subjects.

Familial hypobetalipoproteinaemia (FHBL) is a rare monogenic cause of hypocholesterolaemia. Increased liver transaminase concentrations and hepatic steatosis are a common occurrence in FHBL. Although FHBL subjects are protected against atherosclerotic cardiovascular disease, consequences of fatty liver in FHBL over the longer term are not known. We describe a case in which an obese woman with APOB L343V FHBL developed non-alcoholic steatohepatitis-related cirrhosis of the liver. Given the potential for progression to cirrhosis, it would seem prudent to serially monitor the livers of these individuals using biochemical and imaging techniques, particularly in the presence of known risk factors that lead to further liver injury, such as alcohol and caloric excess.

Familial hypobetalipoproteinemia (FHBL) is a codominant disorder of lipoprotein metabolism characterized by decreased plasma concentrations of LDL-cholesterol and apolipoprotein (apo) B. We examined the effect of heterozygous APOB L343V FHBL on fasting and postprandial lipoprotein metabolism. VLDL, IDL-, and LDL-apoB kinetics were determined in the fasting state using stable isotope methods and compartmental modeling. VLDL-apoB concentrations in FHBL subjects (n=2) were reduced by more than 75% compared to healthy, normolipidemic control subjects ( P P =0.07). ApoB production rates and IDL- and LDL-apoB FCRs were not different between FHBL subjects and controls. To assess postprandial lipoprotein metabolism, a standardized oral fat load was given after a 12 h fast to heterozygous APOB L343V FHBL subjects (n=3) and normolipidemic controls. The postprandial incremental area under the curve (0-10 h) in FHBL subjects was decreased for large TRL-triglyceride (-77%; P P P P P APOB L343V FHBL heterozygotes show decreased TRL production with normal postprandial TRL particle clearance. In contrast, VLDL-apoB production was normal, while the FCR was higher in heterozygotes compared with lean control subjects. These mechanisms account for the marked hypolipidemic state observed in these FHBL subjects.