Phenotype diversity among patients with homozygous familial hypercholesterolemia: A cohort study

Homozygous familial hypercholesterolaemia (HoFH) is a rare disorder usually caused by mutations in both alleles of the low-density lipoprotein receptor gene (LDLR). Premature death, often before the age of 20 years, was a common fate for patients with HoFH prior to the introduction of statins in 1990 and the use of lipoprotein apheresis. Consequently, HoFH has been widely considered a condition exclusive to a population comprising very young patients with extremely high LDL cholesterol (LDL-C) levels. However, recent epidemiologic and genetic studies have shown that the HoFH patient population is far more diverse in terms of age, LDL-C levels, and genetic aetiology than previously realised. We set out to investigate the clinical characteristics regarding age and LDL-C ranges of patients with HoFH.

We analysed the data from 3 recent international studies comprising a total of 167 HoFH patients. The age of the patients ranged from 1 to 75 years, and a large proportion of the patients, both treated and untreated, exhibited LDL-C levels well below the recommended clinical diagnostic threshold for HoFH. LDL-C levels ranged from 4.4 mmol/L to 27.2 mmol/L (170-1052 mg/dL) for untreated patients, and from 2.6 mmol/L to 20.3 mmol/L (101-785 mg/dL) for treated patients. When patients were stratified according to LDLR functionality, a similarly wide range of age and LDL-C values was observed regardless of LDLR mutation status.

These results demonstrate that HoFH is not restricted to very young patients or those with extremely high LDL-C levels.