Subclassification of Phenotypic Homozygous Familial Hypercholesterolemia

Abstract

Homozygous familial hypercholesterolemia (HoFH) is a rare situation where biallelic genetic disturbance of low-density lipoprotein (LDL) metabolism leads to extreme elevation of LDL cholesterol. There is a great variety of severity in their phenotype, where some patients exhibit premature supravalvular aortic stenosis at their early childhood, whereas others experience myocardial infarction at their adolescence. In addition, there is a set of familial hypercholesterolemia (FH) patients whose phenotype fall into between heterozygous FH and HoFH. Recently, the International Atherosclerosis Society reclassified such patients with FH as “severe FH.” Given that we have several different treatment approaches for these FH patients, including those with HoFH, it is quite important to reclassify them according to their severity of phenotype and types of complications. Here, we propose to clarify so-called “phenotypic HoFH” into 3 groups: severe heterozygous FH, typical HoFH, and severe HoFH based on their LDL cholesterol, genetic backgrounds, frequency, residual LDL receptor activity, and their complications.