SEVERE HYPERCHOLESTEROLEMIA - UNUSUAL INHERITANCE IN AN ITALIAN PEDIGREE

A family presenting several cases of severe primary hypercholesterolae mia and/or premature sudden death was studied. This family is characte rized by consanguinity, absence of vertical transmission, bimodal dist ribution of plasma cholesterol values, and reduction of reproductive f itness in affected individuals. The probands have clinical traits of h omozygous familial hypercholesterolaemia, including hypercholesterolae mia, xanthomas and early coronary atherosclerosis, while the parents a nd grandparents are clinically normal. Eight relatives on the mother's side experienced premature sudden death, and in four cases hyperchole sterolaemia was diagnosed. Haplotype segregation analysis of the inher itance of the LDL receptor and apo B genes in the probands' family exc luded the involvement of these two genes in the pathogenesis of the di sease. LDL receptor activity, as well as the ability of LDL to bind to the LDL receptor, and plasma vegetal sterols were within normal limit s both in probands and in their relatives. The study of this pedigree suggests that hypercholesterolaemia is not produced by defects in the LDL receptor or LDL particles, and disease inheritance is consistent w ith an autosomal recessive trait.