Severe Hypercholesterolemia Lipoprotein Lipase Deficiency A Report of a Family with in a Double Heterozygote for (LPLArita) and Apolipoprotein L PLArita

Although heterozygous lipoprotein lipase (LPL) deficiency is not rare, only part of the phenotypes may have been reported in Japan. Here we describe a Japanese family with LPLArita, the most common mutation linked to familial LPL deficiency in Japan, and show for the first time a heterozygote for the mutation who had marked hypercholesterolemia due to increased low-density lipoprotein (LDL) cholesterol. The proband's mother, one of the heterozygotes for LPLArita in the family, had both severe hypercholesterolemia (total cholesterol 306 mg/dl) with an especially increase in LDL-cholesterol and mild hypertriglyceridemia (180 mg/dl). She had normal LDL receptor activity and did not show clear evidence of possible causes of secondary hyperlipidemia. In addition to being heterozygous for LPL deficiency, she was also heterozygous for apo e4. Because the e4 allele is known to be associated with higher LDL-cholesterol, heterozygous apo r4 may be one of causes of her LDL-cholesterol elevation. The other three heterozygotes for LPLArita were moderate drinkers, and all of them had both remarkable hypertriglyceridemia and mild hypercholesterolemia due to increased very-low-density lipoproteins (VLDL). The results suggest that heterozygotes for LPLpita can exhibit various phenotypes of hyperlipidemia, that is, hypertrigliceridemia and/or hypercholesterolemia due to not only increased VLDL but also increased LDL. The phenotypes appear to depend on some other genetic and environmental factors.