PO3-79 UNIQUE CLINICAL PHENOTYPE IN A YOUNG BOY WITH TYPE I HYPERLIPOPROTEINEMIA ASSOCIATED WITH A COMBINED MUTATION ON THE LIPOPROTEIN LIPASE GENE

Abstract

Familial hyperchylomicronemia (type 1 hyperlipoproteinemia) is a rare autosomal recessive disorder characterized by severe chylomicronemia secondary to a congenital deficiency of either lipoprotein lipase or apolipoprotein C-II.1 In 1983, the presence of a lipoprotein lipase inhibitor (which appears to be inherited as an autosomal dominant disease) as an additional cause of this disease was identified.1,2 Familial hyperchylomicronemia generally manifests itself in infancy or early childhood as repeated attacks of abdominal pain and as a creamy appearing (lipemic) plasma, both due to ingestion of dietary fats that have delayed clearance from the plasma. Complications due to hyperehylomicronemia include acute pancreatitis, eruptive xanthomas, lipemia retinalis, and hepatosplenomegaly. Plasma triglyceride concentrations generally range from 1,500 to 4,500 mg/ dl, but levels to 25,000 mg/dl have been reported. The plasma total cholesterol generally ranges from 160 to 400 mg/dl, but may be as high as 1,000 mg/dl when the triglyceride levels are severely elevated. Both low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol usually are exceedingly low, in the range of 20 to 40 mg/dl and 5 to 20 mg/dl, respectively. The fasting plasma very low density lipoprotein (VLDL) cholesterol is elevated, and it increases further after a low-fat, high-carbohydrate diet.3The diagnosis of familial hyperchylomicronemia is based on the presence of a creamy layer (chylomicrons) on the surface of plasma that has been stored in the cold (4 °C), and an elevated plasma triglyceride level. Demonstration of chylomicrons (fasting triglycerides > 1,500 mg/dl) after an overnight fast also may indicate familial hyperchylomicronemia. Analysis of lipoprotein lipase (assay of postheparin plasma) apolipoprotein C-II (gel electrophoresis of VLDL and chylomicron apolipoproteins or lipoprotein lipase activity, or both, in postheparin plasma), and lipoprotein lipase inhibitor activities establish the molecular defect in this disorder.1 Although many reports have appeared describing clinical and biochemical features of familial hyperchylomicronemia, morphologic features of this condition have received little attention. Some morphologic data have been reported in only 5 such patients.4–8 The present report describes clinical and necropsy findings in 4 men with familial hyperchylomicronemia with emphasis on cardiovascular observations.