Type-III Hyperlipoproteinaemia ("remnant removal disease"). Insight into the pathogenetic mechanism

The metabolism of very-low-density lipoprotein (V.L.D.L.) was studied in a patient with type-III hyperlipoproteinaemia. After injection of radioiodinated V.L.D.L. from a donor with endogenous hypertriglyceridaemia (in a type-IV pattern), clearance of radioactivity from the apoprotein-B moiety of V.L.D.L. was slow and appearance in low-density lipoprotein (L.D.L.) was delayed, suggesting defective catabolism of V.L.D.L. in type-III hyperlipoproteinaemia. Despite a 60% increase in the rate of V.L.D.L. production, therapy with oestrogen (ethinyloestradiol 1 microng/kg/day) resulted in a decrease in plasma-lipid concentrations, normalisation of lipoprotein composition, and correction of the defect in V.L.D.L. catabolism with increased conversion to L.D.L. Thus, in type-III hyperlipoproteinaemia, the primary defect seems to be impaired catabolism of V.L.D.L., which is corrected with oestrogen therapy.