Abstract
The association between restless legs syndrome (RLS) and iron homeostasis remains unclear. We compared serum hepcidin and ferritin levels in patients with RLS and controls, and assessed their relationships with RLS phenotype, drug intake, and history of augmentation syndrome. 102 drug-free RLS patients (age 58.9 [24.5–77.2], 63 females) and 73 controls (age 56.8 [23.46–76.6], 45 females) underwent a polysomnography recording. Hepcidin levels were quantified by ELISA. 34 RLS patients had a second assessment after starting dopaminergic drugs. Ferritin level was low (< 50 µg/l) in 14.7% of patients and 25% of controls, with no between-group differences in the mean values. Hepcidin levels were higher in patients even after adjustment for confounding factors, and excluding participants with low ferritin levels. Ferritin and hepcidin levels were comparable before and after treatment, and between patients with (n = 17) and without history of augmentation. Ferritin and hepcidin levels correlated with age, body mass index, and periodic leg movements. Higher hepcidin levels were associated with older age, older age at RLS onset, less daytime sleepiness and familial RLS. In conclusion, serum hepcidin levels but not ferritin were higher in RLS patients regardless of treatment and history of augmentation. Serum hepcidin may be a more relevant biomarker of RLS than ferritin.
Highlights
The association between restless legs syndrome (RLS) and iron homeostasis remains unclear
Body mass index (BMI) as well as the Epworth Sleepiness Scale (ESS), Insomnia Severity Index23 (ISI) and Beck Depression Inventory II (BDI II) scores were higher in patients than controls, indicating higher levels of sleepiness, insomnia and depressive symptoms (Table 1)
This study using a validated enzyme-linked immunosorbent assays (ELISA) assay showed that serum hepcidin levels are higher in patients with RLS compared with healthy controls, in both unadjusted and adjusted models, and after excluding subjects with low ferritin levels
Summary
The association between restless legs syndrome (RLS) and iron homeostasis remains unclear. We compared serum hepcidin and ferritin levels in patients with RLS and controls, and assessed their relationships with RLS phenotype, drug intake, and history of augmentation syndrome. One isolated study showed that low serum ferritin level is a potential biomarker for RLS augmentation[14], one of the most severe complications of this syndrome. But not ferritin, was associated with RLS severity and PLMS9 In this previous study, we quantified bioactive hepcidin-25 using a liquid chromatography-tandem mass spectrometry (LC–MS/MS)-based quantitative method, which is the reference method for peptide quantification. Serum hepcidin levels have never been measured in RLS patients using the easy-to-use ELISA assay, and in the context of iron deficiency, dopaminergic drug intake and recent history of augmentation
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