Restless legs syndrome in children with celiac disease: associations with vitamin D and iron deficiency and the role of gluten-free diet adherence

儿童乳糜泻不宁腿综合征:与维生素D和铁缺乏症的关联以及无麸质饮食依从性的作用

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Abstract

BACKGROUND: Celiac disease (CD) is a systemic autoimmune disorder frequently associated with micronutrient deficiencies and extraintestinal manifestations, including neurological complications. Restless Legs Syndrome (RLS) is a sensorimotor disorder linked to dopaminergic dysfunction and iron and vitamin D deficiency, both of which are common in pediatric CD. OBJECTIVE: To evaluate the prevalence and severity of RLS in children with CD and to investigate the associations between RLS symptoms and serum vitamin D and iron parameters, as well as the potential effect of gluten-free diet (GFD) adherence. METHODS: This prospective cross-sectional study included 67 children with CD (aged 10–18 years) and 68 age- and sex-matched healthy controls. RLS was assessed using the International Restless Legs Syndrome Study Group rating scale. Demographic, anthropometric, clinical, and biochemical data—including serum iron, ferritin, folate, vitamin B12, and 25-hydroxyvitamin D—were recorded. Group comparisons were performed using appropriate parametric or non-parametric tests. Associations were evaluated using Spearman correlation and Bayesian correlation analyses. RESULTS: RLS scores were significantly higher in the CD group compared with controls (median 6 [0–13] vs. 0 [0–0]; p < 0.001), and RLS duration was also longer in children with CD (p < 0.001). Serum vitamin D levels showed a significant negative correlation with RLS scores (r = −0.251, p < 0.05). RLS duration demonstrated a strong positive correlation with RLS severity (r = 0.838, p < 0.001). Transglutaminase IgA levels were inversely correlated with ferritin (r = −0.417, p < 0.001) and folate levels (r = −0.332, p < 0.05), while transglutaminase IgG levels were negatively correlated with ferritin (r = −0.285, p < 0.05) and vitamin D (r = −0.304, p < 0.05). Bayesian correlation analysis revealed no strong associations between Marsh classification and most clinical or biochemical variables, except for a strong association between RLS duration and severity (BF₁₀ > 100). Adherence to a gluten-free diet was not significantly associated with RLS severity (p > 0.05). CONCLUSIONS: Children with celiac disease exhibit significantly higher RLS symptom severity than healthy peers. Lower serum vitamin D levels and reduced iron stores appear to be associated with increased RLS severity, regardless of Marsh stage or dietary adherence. These findings highlight the potential value of screening for RLS and monitoring vitamin D and ferritin levels in pediatric patients with celiac disease.

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