Pediatric sitosterolemia presenting with arthralgia and elevated inflammatory markers mimicking rheumatic disease: two case reports and a review of the literature

Background Sitosterolemia (STSL) is a rare autosomal recessive lipid-storage disorder caused by biallelic loss-of-function variants in ABCG5 or ABCG8, leading to intestinal hyperabsorption and reduced biliary excretion of plant sterols. It is phenotypically heterogeneous; xanthomas, haematological abnormalities and premature atherosclerosis are typical, whereas arthralgia is an under-recognised presenting feature that can mimic rheumatic disease. Case presentation We report two boys (aged 14 and 8 years) who were first evaluated in a paediatric rheumatology department for arthralgia accompanied by cutaneous xanthomas and markedly elevated acute-phase reactants (C-reactive protein 45.8–95 mg/L; erythrocyte sedimentation rate 70–120 mm/h), initially raising suspicion of juvenile idiopathic arthritis. Both had marked hypercholesterolaemia and elevated low-density lipoprotein cholesterol, and serum sitosterol was strikingly raised (44.86 and 727.60 mg/dL; reference ≤0.501 mg/dL). Case 1 additionally showed mild anaemia, giant platelets on the blood smear, right coronary artery dilatation and increased carotid intima–media thickness. Whole-exome sequencing identified biallelic ABCG5 variants in both patients: a homozygous c.1336C > T (p.Arg446Ter) in Case 1, and compound heterozygous c.727C > T (p.Arg243Ter) and c.904 + 1G > A in Case 2; c.727C > T had not previously been reported in the Chinese population. After a low-phytosterol diet and ezetimibe, arthralgia resolved, xanthomas regressed, inflammatory markers normalised and platelet morphology improved over 6 months. Conclusions Sitosterolemia can present with joint symptoms and a pronounced acute-phase response that mimics rheumatic disease. In children with unexplained arthritis accompanied by xanthomas, dyslipidaemia or cytopenias, serum phytosterol profiling and ABCG5/ABCG8 sequencing should be pursued.In these two patients, dietary phytosterol restriction combined with ezetimibe was associated with resolution of arthralgia, regression of xanthomas and normalisation of inflammatory markers over 6 months.