FRI094 Case Report: Treatment Of Sitosterolemia With Ezetimibe - 17 Years Of Follow-up

Disclosure: J.V. Coutinho: None. A.S. Costa: None. M.M. Issa: None. N.P. Paim: None. E.P. Quedas: None. V.S. Nunes: None. A.L. Jorge: None. E.R. Nakandakare: None. A.F. Carrilho: None. Background: Sitosterolemia is a rare autosomal recessive disease caused by inactivating mutations in the ABCG5 or ABCG8 genes. It is characterized by the accumulation of plant sterols in tissues in the form of xanthomas and vascular atheroma. Ezetimibe has been used to decrease serum sterol levels, but its role in xanthomas and arterial atherosclerosis progression remains undetermined. We present a patient diagnosed with sitosterolemia done at age 23 years and followed for 17 years on treatment with ezetimibe 20 mg daily. Clinical case: A 23-year-old man showed typical xanthomas on the extensor surfaces of his hands and Achilles tendons, in addition to splenomegaly and thrombocytopenia. Serum cholesterol and triglyceride levels were normal and sitosterolemia was suspected by a tendon biopsy. The diagnosis was confirmed by high serum concentrations of β-sitosterol and campesterol, and the patient was advised to follow a low plant-sterol diet and to take ezetimibe 20 mg daily. Seven years later, there was no change in xanthoma size, abdominal ultrasound showed normal spleen, and plasma lipid levels were: total cholesterol (TC) 147 mg/dL, HDL cholesterol (HDL) 44 mg/dL, LDL cholesterol (LDL) 61 mg/dL, triglycerides (Tg) 206 mg/dL, desmosterol 0. 137 µg/mL (n < 1.6 µg/mL), lanosterol 0.368 µg/mL (n < 2.2 µg/mL), campesterol 39.65 µg/mL (n < 5.5 µg/mL), β-sitosterol 87.53 µg/mL (n < 1.7 µg/mL) and platelet count 109,000/mL. Seventeen years after diagnosis, at age 40, there was no significant change in xanthoma size and the patient remained without cardiovascular symptoms (normal echocardiography and exercise stress test), however ultrasound showed bilateral carotid-intimal-medial thickening (0.1 on the right and 0.17 on the left, n < 0.1) and serum lipid concentrations were: TC 203 mg/dL, LDL 130 mg/dL, HDL 46 mg/dL, Tg 145 mg/dL, campesterol 21.34 µg/mL (n < 5.5 µg/mL) and β-sitosterol 65.13 µg/mL (n < 1.7 µg/mL). Then, atorvastatin 20 mg daily was added to ezetimibe. In addition, genomic DNA sequencing revealed a compound heterozygous mutation of the ABCG5 gene (NM_022436:exon1:c.64C>T:p.Q22* and NM_022436:exon9:c.1217G>A:p.R406Q). Conclusion: treatment with ezetimibe prevented the growth of xanthomas, however it was not able to normalize plasma levels of campesterol and β-sitosterol. Furthermore, the small carotid intimal-medial thickening found raised the question about the role of plant sterols in atherosclerosis. Presentation: Friday, June 16, 2023