Gene mutations and clinical features of pediatric sitosterolemia

Abstract

Abstract Objective To improve the diagnosis, treatment and follow-up of childhood sitosterolemia by analyzing the phenotypes and genotypes in Chinese pediatric patients with sitosterolemia. Methods The cohort included 26 children with sitosterolemia, 24 of whom underwent genetic testing. Their family history, clinical features, and biochemical indicators, including liver function, blood fat, routine blood test, phytosterol analysis, cardiac and carotid artery ultrasound, fundus examination, genetic analysis results and therapy, were collected and analyzed. Results Among 26 patients, the most common manifestation was xanthomas, which were found in 19 (73.1%). Others were arthralgia (7, 26.9%) and growth retardation (4, 15.4%). Among 24 (92.3%) patients who underwent genetic analysis, 16 (%) had ABCG5 mutations (type 2), and 8 (34.8%) had ABCG8 mutations (type 1). Moreover, the c.1166G > A (p. Arg389His) of ABCG5 was the most hot spot mutation, which was found in 10 patients (66.7%). There were no significant differences in clinical manifestations or laboratory tests between type 1 and type 2 (all p > 0.05). Nonsense mutations were more likely in ABCG5, with a marginally significant difference (p = 0.09), while splicing mutations were more common in ABCG8 (p = 0.01). After diet or conjointed ezetimibe treatment, there was a significant decrease in total cholesterol and low-density lipoprotein cholesterol compared to before treatment. Conclusion In patients with xanthomas and elevated cholesterol, sitosterolemia needs to be considered. Phytosterols and genetic testing should be performed for early diagnosis. Diet control and treatment with ezetimibe can relieve the disease. A larger clinical sample was used to investigate the relationship between genotype and phenotype.