Clinical, genetic characteristics and long-term follow-up of sitosterolemia in children

Sitosterolemia is a rare lipid disorder characterized by elevated phytosterols and low-density lipoprotein cholesterol (LDL-C), resulting from pathogenic variants in the ABCG5 and/or ABCG8 genes. To enhance the understanding of this condition, we systematically summarized the clinical manifestations, laboratory findings, gene variations, and treatment effect outcomes in 12 pediatric patients diagnosed with sitosterolemia. The clinical features, laboratory profiles, and gene variations of 12 children diagnosed with sitosterolemia were analyzed. Long-term follow-up was conducted, with the longest observation period exceeding 8 years. A total of 12 patients with sitosterolemia were diagnosed at our center. The age at diagnosis ranged from 4 months to 8.3 years, with a median age of 1.2 years. Seven patients presented with xanthoma. All patients underwent genetic testing, which revealed ABCG5 variants in 10 patients and an ABCG8 pathogenic variant in one patient; no detectable variants were identified in one patient. Serum sitosterol levels were measured in nine patients, confirming the diagnosis in all cases. Nine patients were managed with a diet low in cholesterol and phytosterols, while three patients received ezetimibe and/or cholestyramine. Long-term follow-up demonstrated reductions in total cholesterol (TC) and LDL-C levels across all patients. Notably, xanthomas resolved in three patients within 1-2 years of treatment, and significant improvement was observed in the remaining four patients. Xanthoma is a hallmark clinical feature in pediatric sitosterolemia, with most cases linked to variants in the ABCG5 gene. Genetic testing and serum phytosterol profiling are essential for diagnosis. Dietary modification alone can achieve favorable outcomes in a substantial number of patients. Furthermore, ezetimibe and cholestyramine have proven effective in managing sitosterolemia in children, contributing to significant clinical improvement.