Endocrine Abstracts

Introduction: Sitosterolemia is a rare lipid disorder characterised by excessive accumulation of phytosterols in the body. There are fewer than 110 cases worldwide, and to our knowledge, there are no reported cases of adult Sitosterolemia from South-East Asia. We report our experience in diagnosing a middle-aged Chinese lady from Singapore with Sitosterolemia.

Case Report: A 45-year-old Chinese lady was referred to the Endocrinology clinic in Oct 2022 by her General Practitioner for possible Familial Hypercholesterolemia (FH). She had first noticed tendon xanthomata on her two children (5-year old daughter; 3-year old son) and brought them for review at another pediatric institution. Investigations for her children revealed very elevated Total Cholesterol (TC) levels (daughter 16 mmol/l; son 8 mmol/l) and Low Density Lipoprotein (LDL) levels, raising the suspicion for FH. Our patient is a non-smoker who consumes a low-fat diet and engages in weekly yoga sessions and runs. She is in a non-consanguinous marriage and does not have a family history of early cardiovascular events or deaths. The father of her 2 children does not have hyperlipidemia. She does not have tendon xanthomata or corneal arcus on examination. She does not have diabetes mellitus, hypertension, thyroid or kidney disorders. She was previously on atorvastatin 10 mg ON, which was increased to atorvastatin 20 mg ON after her first consult with our Endocrinology clinic in October 2022. However, her LDL remained elevated at 4.5 mmol/l and therapy was switched to rosuvastatin 20 mg ON in December 2022. Her LDL remained high at 4.8 mmol/l when rechecked in April 2023 despite compliance to rosuvastatin. She was counselled for and underwent genetic testing for FH. Around this time, the patient’s daughter was found to have elevated plant sterol levels at another institution. We hence switched our patient to ezetimibe 10 mg ON while awaiting the results of her own genetic testing. There was a marked improvement in her LDL levels to 1.9 mmol/l 3 months after switching to ezetimibe monotherapy. Molecular genetic analysis later revealed that she was heterozygous for a variant of the ABCG5 gene c.1166G> A (p.R389H). This variant gene has been implicated in sitosterolemia in which there is a defective ATP-binding cassette transporter leading to decreased gut transport and excretion of plant sterols.

Conclusion: This case illustrates the importance of considering sitosterolemia as a differential apart from familial or polygenic hypercholesterolemia in patients with hyperlipidemia as this would greatly impact subsequent management.