A 36-year-old man comes to the office due to skin lesions on his palms. The patient has yellowish skin nodules over the palmar creases that have been increasing in size and number over the past several years. He also has small clusters of yellow papules on his elbows, knees, and buttocks. His father died of a myocardial infarction at age 56. Biopsy of his lesions shows accumulation of lipid-laden macrophages. Immunoblot analysis suggests a lack of ApoE3 and ApoE4 in his circulating lipoproteins. Which of the following is most likely impaired in this patient?

Question

A 36-year-old man comes to the office due to skin lesions on his palms.  The patient has yellowish skin nodules over the palmar creases that have been increasing in size and number over the past several years.  He also has small clusters of yellow papules on his elbows, knees, and buttocks.  His father died of a myocardial infarction at age 56.  Biopsy of his lesions shows accumulation of lipid-laden macrophages.  Immunoblot analysis suggests a lack of ApoE3 and ApoE4 in his circulating lipoproteins.  Which of the following is most likely impaired in this patient?

Quizplus · Accepted Answer

11ec160b_36c9_35a3_9249_9922372a58e7_MD0001_00 Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) is characterized by xanthomas and premature coronary and peripheral vascular disease. It is an autosomal recessive disorder that is clinically more severe in patients with other conditions affecting lipoprotein metabolism (eg, diabetes, hypothyroidism). The primary defects in familial dysbetalipoproteinemia are in ApoE3 and ApoE4, apolipoproteins found on the triglyceride-rich lipoproteins (chylomicrons and VLDLs) that are responsible for binding hepatic apolipoprotein receptors. Without ApoE3 and ApoE4, the liver cannot efficiently remove chylomicrons and VLDL remnants from the circulation, causing their accumulation in the blood and resultant elevations in cholesterol and triglyceride levels. (Choices A and E) Familial chylomicronemia syndrome is an autosomal recessive disorder characterized by defective lipoprotein lipase activity with increased synthesis and decreased clearance of chylomicron particles (and VLDL to a lesser extent). It can also be due to ApoC2 deficiency because lipoprotein lipase is activated by ApoC2 on chylomicrons and VLDL. (Choice B) ApoA1 is required for esterification of free cholesterol in HDL particles by lecithin-cholesterol acyltransferase (LCAT). ApoA1 and LCAT deficiencies result in low HDL levels and increased circulating free cholesterol levels. (Choice D) Familial hypercholesterolemia is associated with increased levels of LDL cholesterol. It is caused by defects in the ApoB/E LDL receptor or ApoB-100 ligand, leading to decreased hepatic clearance of LDL. Educational objective: Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) is an autosomal recessive disorder characterized by elevated cholesterol and triglyceride levels. It is caused by defects in ApoE3 and ApoE4, leading to decreased clearance of chylomicrons and VLDL remnants. Patients can develop eruptive and palmar xanthomas and premature atherosclerosis.

A 36-Year-Old Man Comes to the Office Due to Skin