Sitosterolemia caused by compound heterozygosis of 2 allelic variants in the ABCG5 gene-21 years of follow-up.

Background: Sitosterolemia is a rare autosomal recessive disease characterized by elevated phytosterol levels in the bloodstream and tissues due to increased absorption and reduced biliary excretion. This condition arises from mutations in one of two genes, ABCG5 or ABCG8, located on chromosome 2p21.

Objective: We report the case of a patient, and his first-degree relatives, diagnosed with sitosterolemia at the age of 23.

Methods: The patient was monitored for 21 years, during which he was advised to adopt a low-plant sterol diet and was treated with ezetimibe.

Results: Over this period, he experienced resolution of splenomegaly and thrombocytopenia, stabilization or reduction in xanthoma growth, and absence of cardiovascular events. Despite these clinical improvements, plasma concentrations of campesterol and β-sitosterol remained above normal levels. Genetic analysis identified two variants in the ABCG5 gene (NM_022436.3): c.64C>T:p.(Gln22*) in exon 1 (rs781098379), a known pathogenic variant, and c.1217G>A p.(Arg406Gln) in exon 9 (rs375364242), described as likely pathogenic.

Conclusion: We propose that the exon 9 variant is indeed pathogenic.