Partial deficiency in lipolysis usually results in only mild disturbances of lipid levels.However, when this is associated with impairment of the uptake of remnant particles and increased production of triglyceride-rich lipoproteins stimulated by environmental factors such as during normal pregnancy, chylomicronemia may ensue.We have previously reported a patient who had approximately 12% of normal LPL activity and developed severe chylomicronemia during pregnancy (Ma et al.1993.J.
Clin.Invest.91: 1953-1958).Here we report four new patients with pregnancy-induced chylomicronemia.In the nonpregnant state, dunk crimson tint these patients had mild to modest elevation of triglyceride levels ranging from 80 to 623 mg/dl (0.
9-7.0 mmol/l) but during the third trimester they became severely chylomicronemic with triglyceride levels ranging from 2314 to 14,596 mg/dl (26 to 164 mmol/l).Three of these four patients had partial lipoprotein lipase (LPL) deficiency.The molecular characterization of the LPL gene in these three patients with partial LPL deficiency revealed four novel unpublished mutations.Patient #1 is gotrax rear fender a compound heterozygote for Leu252Arg and Ala261Thr mutations which are associated with 25% of normal LPL activity.
In addition, she has an apoE3/2 genotype.Patient #2 is a heterozygote for a Asn291Ser substitution with 69% of LPL activity and also has an apoE3/2 genotype, while patient #3 is a heterozygote for a Trp382Stop mutation with 54% of normal LPL activity and has an apoE4/2 genotype.The fourth patient (#4) with pregnancy-induced chylomicronemia does not have LPL deficiency and has an apoE3/3 genotype.The previously reported patient (#5) who had 12% of normal LPL activity due to homozygosity for a Ser172Cys mutation also has an E3/3 genotype.Our data suggest that mutations in the LPL gene that cause partial LPL deficiency might be a frequent factor in the pathogenesis of pregnancy-induced chylomicronemia.