Characterization of the unique Chinese W483X mutation in the low-density lipoprotein-receptor gene in young patients with homozygous familial hypercholesterolemia.

BACKGROUND: Recent 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.

OBJECTIVE: We 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.

METHODS: A 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.

RESULTS: Two 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%.

CONCLUSIONS: The results suggest that younger HoFH patients with W483X mutations had a severe phenotype and should receive more aggressive treatment.