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Background-Patients with homozygous familial hypercholesterolemia (hmzFH) attributable to LDL receptor gene mutations have shown a remarkable increase in survival over the last 20 years. Early onset coronary heart disease (CHD) and calcific aortic valve stenosis are the major complications of this disorder. We now report extensive premature calcification of the aorta in patients with hmzFH. Methods and Results-We examined 25 hmzFH patients from Canada; mean age was 32 years (range 5 to 54), and mean baseline cholesterol before treatment was 19Ϯ5 mmol/L (737Ϯ206 mg/dL). Aortic calcification was quantified using computed tomography (CT

The fractional rate of cholesterol esterification in very low density lipoprotein-and low density lipoprotein-depleted plasma (FERgoJ was studied in normolipidemic subjects and in individuals with hyperlipidemia and proven coronary artery disease (CAD). The FERnm, was significantly higher than the FER in whole plasma and was significantly higher in normal men than in normal women. In addition, men and women with primary hyperlipidemia had significantly

Normal pregnancy is associated with a two-to threefold increase in plasma triglyceride levels, particularly in the third trimester, due both to the overproduction of VLDLs and to the possible suppression. of lipoprotein lipase (LPL) activity. Numerous mutations in the human LPL gene causing complete LPL deficiency have been described, but naturally occurring mutations that result in defective LPL with partial activity have not yet been reported. Here we describe a 30-yr-old woman who was first diagnosed with LPL deficiency during pregnancy after she developed pancreatitis. Her plasma triglyceride levels remained mildly elevated at approximately 300 mg/dl (3.4 mmol/liter) after the first pregnancy but rose significantly after she became pregnant again (1800 to 2000 mg/dl) (20.2 to 22.5 mmol/liter). DNA sequence analysis of the LPL gene showed that the patient is homozygous for a Ser '72-Cys missense mutation in exon 5. In vitro mutagenesis revealed that the Ser '72-*uCys mutation caused a mutant LPL protein that had residual activity higher than that seen in all eight other missense mutations in patients with LPL deficiency identified in our laboratory. We propose that some mutations in the LPL gene produce a defective LPL with partial activity, which usually leads to mild hypertriglyceridemia. (J. Clin. Invest.

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