Clinical, genetic profile and therapy evaluation of 55 children and 5 adults with sitosterolemia

Background: Sitosterolemia is a rare autosomal recessive disease characterized by phytosterol accumulation in the blood and tissues. However, the detailed clinical and genetic spectra are lacking. Objective: To describe and compare the clinical, biochemical, genetic, therapeutic, and follow-up characteristics of 55 pediatric and five adult sitosterolemia patients. Methods: Clinical, genetic and therapeutic data from 60 patients at Xinhua Hospital from January 2016 to June 2021 were retrospectively collected. ders(30%), arthralgia(24%), splenomegaly(11%), atherosclerosis (10%). Adult patients had symptoms such as atherosclerosis (5/5), xanthomas(4/5), hematological disorders(3/5), arthralgia(3/5), splenomegaly(3/5). Elevated total cholesterol(TC) and low-density lipoprotein cholesterol(LDL-C) were observed in 96% patients (pediatric 98%, adult 3/4), and phytosterol levels in 100% patients. The age of onset was also negatively correlated with blood TC ( P < 0.0001, r = -0.5548) and LDL-C ( P = 0.0001, r = -0.4859) levels. Targeted treatments resulted in symptomatic remission(pediatric 96%, adult 4/5), and significantly decreased lipid and phytosterol levels(all P < 0.05). In the dietary-therapy cohort(n = 34), blood lipid levels decreased(all P < 0.05). In the 13 pediatric patients from the dietary-therapy cohort who switched from dietary to combination therapy with ezetimibe, dietary therapy decreased TC and LDL-C levels by 54% and 52%, and ezetimibe further decreased them by 18% and 20%, respectively. Further, we identified 15 novel ABCG5 / ABCG8 variants. Conclusions: This study expands the clinical and genetic spectra of sitosterolemia. The lowphytosterol diet is the cornerstone of sitosterolemia treatment. Ezetimibe can further decrease blood lipid levels and increase daily dietary phytosterol tolerance. (c) 2021 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Automated summary

This study describes and compares the clinical, biochemical, genetic, therapeutic, and follow-up characteristics of pediatric and adult patients with sitosterolemia. The results show that dietary therapy and ezetimibe can effectively alleviate symptoms and reduce blood lipid levels. The study also identified 15 novel ABCG5/ABCG8 gene variants.