Clearance defects in primary chylomicronemia: a study of tissue lipoprotein lipase activities.

Tissue and postheparin lipoprotein lipase (LPL) activities were assayed in a heterogeneous group of eight chylomicronemic subjects ranging in age from 15 years to 55 years. Three patients, presenting with the classical genetic and clinical features of type I hyperlipoproteinemia, had virtually absent adipose tissue LPL activity and markedly reduced muscle LPL activity (between 5% and 20% of normal). A fourth patient, with a similar but more benign lipoprotein and clinical phenotype, showed reduced adipose tissue LPL activity (10% of control) but retained essentially normal muscle enzyme. This patient represents a variant form of familial LPL deficiency. Two of the four remaining patients presented with typical features of adult type V hyperlipoproteinemia associated with familial hypertriglyceridemia (type IV and V phenotypes) in first-degree relatives. Adipose tissue LPL activities were 25% to 35% of the control mean in these patients, but muscle activities were normal or elevated. A third patient had suggestively similar tissue enzyme levels, but a family study could not be carried out. The eighth patient presented with a brittle type V phenotype, normolipidemia in the two first-degree relatives available for study and normal lipolytic activity in adipose tissue, muscle, and postheparin plasma assayed against a 14C-triolein substrate. An oral fat load in this patient, however, led to a marked but transient increase in light scattering suggesting defective clearance. Mixing experiments in vitro using a chylomicron substrate strongly suggested an extrinsic defect of lipolysis due to the inhibitory effect of excess very low density lipoprotein peptides, presumably apo C-III.(ABSTRACT TRUNCATED AT 250 WORDS)