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.
Results: Pediatric patients' manifestations included xanthomas(93%), hematological disorders(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 low-phytosterol diet is the cornerstone of sitosterolemia treatment. Ezetimibe can further decrease blood lipid levels and increase daily dietary phytosterol tolerance.
Keywords: ABCG5; ABCG8; Hypercholesterolemia; Phytosterols; Sitosterolemia; Variant.
Copyright © 2021. Published by Elsevier Inc.