ESPE Abstracts

Background: Sitosterolemia, a rare autosomal recessive defect in lipid metabolism, is caused by mutations in the transporter genes ABCG5 and ABCG8 coding receptors on the luminal surface of enterocytes. Thus, hyperabsorption of non-digestible plant sterol in tissue and blood resulting in cardiovascular (CVD) sequalae. Here we report a case of Sitosterolaemia incidentally diagnosed on whole exome sequencing (WES) for bony lesions in a young Saudi girl with asymptomatic presentation and good response to diet restriction and Ezetimibe on one year follow up.

Case description: A healthy 6 years old girl, referred to the endocrine service, for assessment of bony lesions and café au lait spots noted by family after minimal trauma. Clinical examination and biochemical workup for McCune Albright was negative. WES showed a missense pathogenic heterozygous variant in EXT1 (c.1019G>A) p. (Arg340His) and incidental nonsense pathogenic homozygous variant in ABCG5 (c.1336C>T) p. (Arg446*). The former causing Hereditary Multiple Exostoses, explaining the bony lesions. Patient remained clinically asymptomatic, apart from mild self-resolving skin bruises. Skin examination was normal without cutaneous manifestations of hyperlipidaemia. Initial lipid screening showed[fn1]: (TC) 5.0 mmol/L, (LDL-C) 3.69 mmol/L, (HDL-C) 1.05 mmol/L and (TG) 1.67 mmol/L. Baseline cardiovascular evaluation; including ECG, echocardiography and intimal-media thickness via cervical vascular ultrasonography was normal. Initial haematological evaluation revealed no haemolytic anaemia with normal platelet count and function. Gradually increasing LDL-C trend, reaching 5.56 mmol/L, showed response to both plant-sterol restricted diet and Ezetimibe. Cascade screening of immediate family revealed heterozygous carrier state in parents and younger siblings, a homozygous mutation in older sister who was clinically asymptomatic but started on Ezetimibe and diet control for elevated LDL-C.

Conclusion: Sitosterolaemia has variable expressivity, ranging from nearly asymptomatic to severe hypercholesterolemia, accelerating atherosclerosis and premature cardiac mortality risk. Diagnosis is challenging and should be confirmed by genetic testing. Dietary restriction and once-daily Ezetimibe medication were effective in our case. Monitoring plant sterol levels pre and post intervention would have been helpful, likely reducing CVD risk progression, if it had been readily available. Given that proper management can improve disease's prognosis, early detection and timely intervention are crucial.

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