Phenotypes, Genotypes, Treatment, and Outcomes of 14 Children with Sitosterolemia at Vietnam National Children's Hospital.

Background: Sitosterolemia is a rare autosomal recessive disorder characterized by diverse clinical manifestations ranging from asymptomatic cases to the development of xanthomas, hypercholesterolemia, premature atherosclerosis, or even sudden death during childhood. It results from homozygous or compound heterozygous pathogenic variants in the ABCG5 or ABCG8 genes. Prompt detection and intervention are essential to managing this condition and preventing severe outcomes. Methods: This study aims to retrospectively analyze the phenotype, genotype, treatment, and outcomes of 14 children-seven boys and seven girls-all of Vietnamese origin, diagnosed with sitosterolemia at the Vietnam National Children's Hospital between March 2015 and July 2024. Results: The median ages at disease onset and diagnosis were 5.7 years (range: 1.5-17.9) and 7.2 years (range: 1.7-17.9), respectively. Xanthomas were observed in 85.7% of patients (12/14), arthralgia in 14.3% (2/14), and anemia in 7.1% (1/14), with no cases of thrombocytopenia. At diagnosis, all patients exhibited elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), with considerably higher levels in patients with xanthomas compared to those without. Mutations in the ABCG5 gene were identified in 71.4% (10/14) of the patients, while 28.6% (4/14) had mutations in the ABCG8 gene. Fourteen variants were detected, nine in ABCG5 and five in ABCG8, with five variants reported for the first time in sitosterolemia patients. Initial management for all patients involved dietary modifications. After three months, 10 patients with persistently elevated TC and LDL-C received ezetimibe or cholestyramine treatment. Among the eight patients who continued treatment for over three months, the median TC and LDL-C concentrations decreased by 54.9% and 67.3%, respectively. Conclusions: Among Vietnamese patients with sitosterolemia, variants in the ABCG5 gene were more prevalent than those in the ABCG8 gene. Patients showed a positive response to ezetimibe or cholestyramine treatment. Genetic testing is essential for establishing a diagnosis of sitosterolemia and guiding accurate management strategies.