At this point, having reviewed the molecular and genetic bases for the heterogeneity of the clinical presentations of hypercholesterolemia, we are left with some important questions. This Figure addresses the "milder" cases of elevated LDL-C, in patients with at least one functional LDL receptor allele. Based on classical clinical presentations, heterozygous FH has an estimated prevalence of 1 in 500 persons in the United States - but this estimate was not based on population-based sequencing. It is at least conceptually possible that milder LDL receptor mutations might cause hypercholesterolemia that would not conventionally be viewed as classic heterozygous FH. So the questions are
- could the prevalence of heterozygous FH actually be higher than one in 500? and
- could some patients with the severe hypercholesterolemia - for example,
the patient
case presented in the Figure 2 - actually have two LDL
receptor mutations?
