Purpose of review: This review focuses on recent advances in the management of patients with homozygous familial hypercholesterolaemia, autosomal recessive hypercholesterolaemia and familial defective apolipoprotein B.
Recent findings: Autosomal recessive hypercholesterolaemia has been described as a 'phenocopy' of homozygous familial hypercholesterolaemia. Although the clinical phenotypes are similar, autosomal recessive hypercholesterolaemia seems to be less severe, more variable within a single family, and more responsive to lipid-lowering drug therapy. The cardiovascular complications of premature atherosclerosis are delayed in some individuals and involvement of the aortic root and valve is less common than in homozygous familial hypercholesterolaemia. Apheresis is still the treatment of choice in homozygous familial hypercholesterolaemia and in autosomal recessive hypercholesterolaemia patients in whom maximal drug therapy does not achieve adequate control. In addition to the profound cholesterol-lowering effects of apheresis, other potentially beneficial phenomena have been documented: improved vascular endothelial function and haemorheology, reduction in lipoprotein (a) and procoagulatory status, and a decrease in adhesion molecules and C-reactive protein.
Summary: Patients with severe homozygous hypercholesterolaemia illustrate the natural history of atherosclerosis within a condensed timeframe. Effective cholesterol-lowering treatment started in early childhood is essential to prevent onset of life-threatening atherosclerotic involvement of the aortic root and valve, and the coronary arteries. Noninvasive methods for regular monitoring of the major sites involved in the atherosclerotic process are necessary in patients with no symptoms or signs of ischaemia. Management of patients with severe homozygous hypercholesterolaemia continues to be a major challenge.