Metabolic studies in an unusual case of asymptomatic familial hypobetalipoproteinemia with hypoalphalipoproteinemia and fasting chylomicronemia

A new kindred with asymptomatic hypobetalipoproteinemia is reported. The proband, age 67, differs from previously described cases in several respects: (a) unusually low levels of low density lipoprotein (LDL) cholesterol (4-8 mg/dl); (b) normal triglyceride levels; (c) low levels of high density lipoprotein; (d) mild fat malabsorption; and (e) a defect in chylomicron clearance. On a high-carbohydrate diet his plasma triglyceride levels, instead of rising, actually fell. Turnover of triglycerides in very low density lipoproteins (VLDL) was low (2.8 mg/kg per h). Fractional catabolic rate of LDL protein was just above the normal range (0.655/d) but net turnover was <10% of normal (0.65 mg/kg per d). The half-life of his chylomicrons was 29 min, five times the normal value. Postheparin liporoteins lipase activity was normal and apolipoprotein C-II the activator protein for lipoprotein lipase, was present and functional. Apolipoprotein C-III₁, however, was not detected in the VLDL fraction, a finding previously reported in patients with abetalipoproteinemia. Fecal excretion of cholesterol was almost twice normal; total sterol balance was increased by ≃40%. The unusual features in the proband that distinguish him from previously described cases and from his affected first-degree relatives, suggested that, in addition to the basic gene defect affecting LDL metabolism, he might have a second abnormality affecting clearance of chylomicrons and VLDL. The ratio of apolipoprotein E₃ to E₂ in his VLDL fraction was 0.93, just below the lower limit of normal, suggesting heterozygosity for E₃ deficiency. Whether or not this contributes to his hypertriglyceridemia remains to be established.