Case report: The first report of a family with sitosterolemia in the Polish population.

BACKGROUND

Sitosterolemia is a rare autosomal recessive lipid disorder caused by mutations in the ABCG5 or ABCG8 genes, resulting in excessive intestinal absorption and impaired biliary excretion of plant sterols, which leads to their accumulation in plasma and tissues. Clinical manifestations include premature coronary artery disease, liver dysfunction, hepatosplenomegaly, and hematologic abnormalities.

OBJECTIVE

We report the first Polish family diagnosed with sitosterolemia.

METHODS

A 19-year-old male patient with severe hypercholesterolemia and resistance to statin therapy and his family members were examined, including biochemical and imaging studies, serum sterol assessment by gas chromatography-mass spectrometry, and genetic testing using next-generation sequencing of genes involved in lipid metabolism.

RESULTS

The proband presented with total cholesterol of 8.0 mmol/L, low-density lipoprotein cholesterol of 5.80 mmol/L, high-density lipoprotein cholesterol of 1.24 mmol/L, and triglycerides of 2.38 mmol/L. Genetic analysis revealed 2 variants in the ABCG8 gene in the patient and his brother: a pathogenic variant c.1083G>A (p.Trp361Ter), present in the patient's father, and a variant of uncertain significance c.1534G>A (p.Gly512Arg), present in the patient's mother. Serum sterol concentrations in the patient were markedly elevated, including campesterol (139.8 µmol/L), stigmasterol (2.2 µmol/L), isofucosterol (56.9 µmol/L), and sitosterol (333.9 µmol/L). Introduction of ezetimibe therapy combined with a low-plant sterol diet resulted in improvement of the lipid profile.

CONCLUSION

These findings highlight the role of genetic testing and serum sterol measurement in the differential diagnosis of inherited lipid disorders, especially in patients with statin-resistant hypercholesterolemia. Early diagnosis of sitosterolemia is important to introduce an appropriate diet and pharmacotherapy.