Heterozygous lipoprotein lipase deficiency due to a missense mutation as the cause of impaired triglyceride tolerance with multiple lipoprotein abnormalities.

In 16 members of two Austrian families affected by a missense mutation at codon 188 of the lipoprotein lipase (LPL) gene (8 heterozygous and 8 normal subjects), carrier status for the mutation as determined by DNA analysis was related to LPL activ- ity in postheparin plasma, to the magnitude of postprandial lipemia, and to concentration, composition, and size of the ma- jor lipoprotein classes ofpostabsorptive plasma. Carriers exhib- ited clearly reduced LPL activity, normal fasting triglycerides, but pronounced postprandial lipemia. The carriers' impaired triglyceride tolerance, as evident in the postprandial state of challenge only, was associated with a fasting lipoprotein con- stellation characterized by (a) enrichment ofHDL2 with triglycerides, (b) reduced HDL2-cholesterol, (c) enrichment of VLDL and intermediate density lipoprotein (IDL) with choles- teryl esters, (d) elevated IDL levels, and (e) small-sized LDL. Within any given individual, the degrees of expression of these characteristics were quantitatively and continuously related with each other as well as with the magnitude of lipemia and with LPL activity. (J. Clin. Invest. 1993. 91:448-455.) Key words: high-density lipoprotein 2 * intermediate-density lipoprotein* low-density lipoprotein -lipoprotein lipase * postpran- dial lipemia gene spanning -30 kb of chromosome 8, with its coding se- quence split into 10 exons, and is produced mainly in fat and muscle cells (4-7). To allow interactions between the enzyme and circulating triglyceride (TG)-rich lipoproteins, LPL is se-