Autosomal recessive hypercholesterolemia in three sisters with phenotypic homozygous familial hypercholesterolemia: diagnostic and therapeutic procedures.

Familial hypercholesterolemia is an autosomal-dominant inherited disorder caused by mutations in the low-density lipoprotein (LDL) receptor gene. The homozygous form is characterized by high-serum LDL cholesterol concentrations, xanthoma formation and premature atherosclerosis. Recently, another molecular defect that also results in severely elevated LDL cholesterol levels was identified: autosomal recessive hypercholesterolemia. This inherited disorder is caused by a mutation in a putative LDL receptor adaptor protein. In our lipid clinic, three sisters with phenotypic homozygous hypercholesterolemia were recently diagnosed as having autosomal recessive hypercholesterolemia. They presented in 1990 with massive tuberous xanthomas at the knees, thighs, elbows and buttocks. LDL receptor and apolipoprotein B gene defects were excluded through mutation analysis. From 1992 onward they underwent LDL-apheresis on a weekly basis. To date the clinical outcome is very satisfying with no evidence of coronary heart disease or aortic valve lesions and almost complete regression of xanthomatosis.