Are serum ferritin and transferrin saturation risk markers for restless legs syndrome in young adults? Longitudinal and cross‐sectional data from the Western Australian Pregnancy Cohort (Raine) Study

Lammers, Natasja; Curry‐Hyde, Ashton; Smith, Anne; Eastwood, Peter R.; Straker, Leon; Champion, G. David; McArdle, Nigel

doi:10.1111/jsr.12741

Cited by 12 publications

(5 citation statements)

References 40 publications

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“…Despite the absence of standardized cut-offs for serum hepcidin levels, high serum hepcidin levels (≥ 20.99 ng/mL) were associated with older age, older age at RLS onset, positive family history of RLS, lower excessive daytime sleepiness; however these results should be taken with caution regarding the multiple testing performed and the sample size of the population. The best hepcidin cut Although serum ferritin is considered as the most informative RLS biomarker, in our study ferritin level was not different between patients with RLS and controls, as previously reported [9][10][11][12][13] . Moreover, the percentage of subjects with ferritin level < 50 ng/mL was similar in the RLS and control groups.…”

Section: Discussionsupporting

confidence: 72%

Hepcidin and ferritin levels in restless legs syndrome: a case–control study

Chenini

Delaby

Rassu

et al. 2020

Sci Rep

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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 drugfree 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. Restless legs syndrome (RLS) is a frequent sensorimotor disorder that often impairs sleep and quality of life 1, 2. RLS is associated with periodic leg movements in sleep (PLMS) in 80% of cases 3. Genetic burden, iron deficiency and dopamine dysregulation play a major role in the pathogenesis of RLS and PLMS 4-6. Several neuropathological, biological, and brain-imaging studies have found iron deficiency in the brain and cerebrospinal fluid of patients with RLS 7. However, the cause of such deficiency is still unclear. Serum ferritin level is considered as a good biomarker of iron stores 8. Although iron deficiency has been associated with RLS pathogenesis, low serum ferritin has only been reported in 10-20% of adults with RLS 7. Moreover, recent large clinical and population-based studies did not confirm the association between RLS and serum ferritin levels 9-13. 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. Augmentation is a treatment-induced paradoxical worsening of RLS symptoms caused by long-term high dose dopaminergic therapy, and remains the major challenge of RLS management 14-16. Hepcidin is the main regulator of iron homeostasis 17 , by modulating the internalization and degradation of the iron-exporter ferroportin, and thus inhibiting iron absorption from the gut and iron release from storage sites. Consequently, hepcidin has emerged as a strong biomarker for the diagnosis and monitoring of a large spectrum of iron-related disorders 18. As a dynamic iron regulator, high hepcidin expression will decrease plasma iron levels, whereas lo...

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Section: Discussionsupporting

confidence: 72%

Hepcidin and ferritin levels in restless legs syndrome: a case–control study

Chenini

Delaby

Rassu

et al. 2020

Sci Rep

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“…Currently, serum ferritin is used to guide treatment, but we have discussed the concerns regarding the utility of serum ferritin both as a measure of total body iron stores and serum ferritin levels are of no value in predicting response to treatment. Lammers et al studied serum ferritin, bodily iron, and RLS, finding no association between early-onset RLS and longitudinal measures of iron stores [136]. Similarly, while serum ferritin is currently used clinically to guide treatment, it has been shown that serum ferritin levels have no predictive value in the response to treatment [131].…”

Section: Ferritin As a Disease Biomarkermentioning

confidence: 99%

Emerging and Dynamic Biomedical Uses of Ferritin

Chiou

Connor

2018

Pharmaceuticals

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Ferritin, a ubiquitously expressed protein, has classically been considered the main iron cellular storage molecule in the body. Owing to the ferroxidase activity of the H-subunit and the nucleation ability of the L-subunit, ferritin can store a large amount of iron within its mineral core. However, recent evidence has demonstrated a range of abilities of ferritin that extends well beyond the scope of iron storage. This review aims to discuss novel functions and biomedical uses of ferritin in the processes of iron delivery, delivery of biologics such as chemotherapies and contrast agents, and the utility of ferritin as a biomarker in a number of neurological diseases.

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“…[ 22 ] It is not clear whether RLS is related to low iron levels in the peripheral or central nervous system (CNS). Early evidence suggests that the severity of RLS increases with a decrease in peripheral iron, which may be related to the level of peripheral iron [ 23 ] and that the morbidity of RLS is higher in patients with peripheral iron deficiency. [ 24 ] However, recent findings have challenged these findings, with a population-based study establishing that RLS is not associated with plasma ferritin levels.…”

Section: Pathophysiologymentioning

confidence: 99%

Exploration of restless legs syndrome under the new concept: A review

2022

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Restless leg syndrome (Restless legs syndrome, RLS) is a common neurological disorder. The pathogenesis of RLS remains unknown, and recent pathophysiological developments have shown the contribution of various genetic markers, neurotransmitter dysfunction, and iron deficiency to the disease, as well as other unidentified contributing mechanisms, particularly chronic renal dysfunction. RLS enhancement syndrome is frequently observed in patients with RLS who have received long-term dopamine agonist therapy, manifesting as a worsening of RLS symptoms, usually associated with an increase in the dose of dopamine agonist. Some patients with RLS can adequately control their symptoms with non-pharmacological measures such as massage and warm baths. First-line treatment options include iron supplementation for those with evidence of reduced iron stores, or gabapentin or pregabalin, as well as dopamine agonists, such as pramipexole. Second-line therapies include opioids such as tramadol. RLS seriously affects the quality of life of patients, and because its pathogenesis is unclear, more biological evidence and treatment methods need to be explored.Abbreviations: BID = brain iron deficiency, CNS = central nervous system, GABA = gamma-aminobutyric acid, IRLSSG = International restless leg syndrome research group, PLMD = periodic limb movement disorder, PLMS = periodic leg movement in sleep, RLS = restless legs syndrome, WED = Willis-Ekbom disease.

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Are serum ferritin and transferrin saturation risk markers for restless legs syndrome in young adults? Longitudinal and cross‐sectional data from the Western Australian Pregnancy Cohort (Raine) Study

Cited by 12 publications

References 40 publications

Hepcidin and ferritin levels in restless legs syndrome: a case–control study

Hepcidin and ferritin levels in restless legs syndrome: a case–control study

Emerging and Dynamic Biomedical Uses of Ferritin

Exploration of restless legs syndrome under the new concept: A review

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