Characterization of the unique Chinese W483XÂ mutation in the low-density lipoprotein-receptor gene in young patients with homozygous familial hypercholesterolemia

•The LDLR W483X mutation is the common mutation in the Chinese FH population.•Atherosclerosis progressed rapidly in younger HoFH patients with the W483X mutation.•These young patients should receive more aggressive treatment as early as possible.

BackgroundRecent guidelines suggest that more attention should be focused on children with homozygous familial hypercholesterolemia (HoFH). China may have 3.8 million potential FH patients, but there are limited data focused on HoFH children.ObjectiveWe systematically analyzed the characteristic phenotype and the relationship between the genotype and the phenotype in HoFH children with the unique Chinese W483X mutation in the low-density lipoprotein (LDL)-receptor gene.MethodsA systematic retrospective analysis of the lipid and cardiovascular characteristics of HoFH patients in the atherosclerosis clinic of Beijing Anzhen Hospital was performed. The W483X mutation was confirmed using DNA sequencing of the patients and their parents.ResultsTwo HoFH and 9 compound heterozygous patients (mean age = 14.7 years) with 2 novel mutations, Q254X and c.1363delC, were found. In total, 81.8% of the patients were from southern China. All the patients had xanthoma, and the average TC and LDL-C levels were 16.8 and 14.4 mmol/L, respectively. Echocardiography showed that 63.6% of the patients had aortic calcification, and 54.5% had mild regurgitation of the aortic valve. The coronary flow velocity reserve had a mean value of 2.12, and the cIMT was 0.17 cm. The follow-up period was between 3 months and 8 years. Although all the patients began the lipid-lowering treatment, 2 patients died because of severe cardiovascular disease. The LDL-C levels of 6 patients were slightly decreased by approximately 21% and remained far from the target values, and the other 3 patients' LDL-C levels increased by 13%.ConclusionsThe results suggest that younger HoFH patients with W483X mutations had a severe phenotype and should receive more aggressive treatment.