Family study in familial hypercholesterolemia with a receptor-negative homozygous 9-year-old boy

A 2-year-old boy showed massive xanthomas, especially tendon xanthomas and cutaneous xanthomas on the knees. When presented to us at the age of 9 years, his total cholesterol was 700-1100 mg/dl, LDL-cholesterol 600-1000 mg/dl, and triglycerides were normal, which is the constellation of hyperlipoproteinemia type IIa. LDL receptor studies showed 3% of normal binding activity, which defines the receptor-negative form of homozygous familial hypercholesterolemia (FH). Remarkably there was no sign of coronary heart disease in angiography. Three great-grandparents and the paternal grandfather (at 44 years) died from cardiovascular disease. The maternal grandmother is heterozygote for FH as well as three siblings of the father. In all family members we determined apolipoprotein B, apo-E-phenotype and the lipoprotein fraction Lp (a). In this family there seems to be no genetic coupling between the LDL receptor gene and the gene for Lp (a).- Therapy of heterozygous FH should start as early as possible, before symptoms appear. Therefore pediatricians should be very critical about the cholesterol values of their little patients.