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      Iron’s role in paediatric restless legs syndrome – a review

      , ,
      Paediatrics & Child Health
      Oxford University Press (OUP)

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          Abstract

          Paediatric restless legs syndrome (RLS) treatment is important because RLS's associated sleep disturbance causes significant developmental-behavioural morbidity and impacts family well-being. RLS is associated with brain iron insufficiency and dopaminergic dysfunction. Diagnosis requires fulfillment of diagnostic criteria, which for children are currently in evolution, and have limitations, especially in preschoolers. The community physician needs to recognize the possibility of RLS to refer to a sleep specialist for diagnostic confirmation and management recommendations, which include oral iron therapy, even though there is currently no definitive research evidence for iron efficacy in most children with RLS. A 3 mg to 6 mg elemental iron/kg/day dose for three months could be tried if the ferritin level is <50 ug/L. Sleep hygiene and behavioural strategies are also recommended. Iron supplementation should be safe in the absence of iron metabolism disorders, provided that transferrin saturation and ferritin levels are monitored pre-and post-treatment.

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          Most cited references18

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          A genetic risk factor for periodic limb movements in sleep.

          The restless legs syndrome (RLS) is a common neurologic disorder characterized by an irresistible urge to move the legs. It is a major cause of sleep disruption. Periodic limb movements in sleep are detectable in most patients with RLS and represent an objective physiological metric. To search for sequence variants contributing to RLS, we performed a genomewide association study and two replication studies. To minimize phenotypic heterogeneity, we focused on patients with RLS who had objectively documented periodic limb movements in sleep. We measured serum ferritin levels, since iron depletion has been associated with the pathogenesis of RLS. In an Icelandic discovery sample of patients with RLS and periodic limb movements in sleep, we observed a genomewide significant association with a common variant in an intron of BTBD9 on chromosome 6p21.2 (odds ratio, 1.8; P=2x10(-9)). This association was replicated in a second Icelandic sample (odds ratio, 1.8; P=4x10(-4)) and a U.S. sample (odds ratio, 1.5; P=4x10(-3)). With this variant, the population attributable risk of RLS with periodic limb movements was approximately 50%. An association between the variant and periodic limb movements in sleep without RLS (and the absence of such an association for RLS without periodic limb movements) suggests that we have identified a genetic determinant of periodic limb movements in sleep (odds ratio, 1.9; P=1x10(-17)). Serum ferritin levels were decreased by 13% per allele of the at-risk variant (95% confidence interval, 5 to 20; P=0.002). We have discovered a variant associated with susceptibility to periodic limb movements in sleep. The inverse correlation of the variant with iron stores is consistent with the suspected involvement of iron depletion in the pathogenesis of the disease. Copyright 2007 Massachusetts Medical Society.
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            Effects of iron supplementation on attention deficit hyperactivity disorder in children.

            Iron deficiency has been suggested as a possible contributing cause of attention deficit hyperactivity disorder (ADHD) in children. This present study examined the effects of iron supplementation on ADHD in children. Twenty-three nonanemic children (aged 5-8 years) with serum ferritin levels <30 ng/mL who met DSM-IV criteria for ADHD were randomized (3:1 ratio) to either oral iron (ferrous sulfate, 80 mg/day, n = 18) or placebo (n = 5) for 12 weeks. There was a progressive significant decrease in the ADHD Rating Scale after 12 weeks on iron (-11.0 +/- 13.9; P < 0.008), but not on placebo (3.0 +/- 5.7; P = 0.308). Improvement on Conners' Parent Rating Scale (P = 0.055) and Conners' Teacher Rating Scale (P = 0.076) with iron supplementation therapy failed to reach significance. The mean Clinical Global Impression-Severity significantly decreased at 12 weeks (P < 0.01) with iron, without change in the placebo group. Iron supplementation (80 mg/day) appeared to improve ADHD symptoms in children with low serum ferritin levels suggesting a need for future investigations with larger controlled trials. Iron therapy was well tolerated and effectiveness is comparable to stimulants.
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              Iron status and restless legs syndrome in the elderly.

              The relationship between iron status and the restless legs syndrome (RLS) was examined in 18 elderly patients with RLS and in 18 matched control subjects. A rating scale with a maximum score of 10 was used to assess the severity of RLS symptoms. Serum ferritin levels were reduced in the RLS patients compared with control subjects (median 33 micrograms/l vs. 59 micrograms/l, p 18 micrograms/l, 45 micrograms/l, < 100 micrograms/l. Iron deficiency, with or without anaemia, is an important contributor to the development of RLS in elderly patients, and iron supplements can produce a significant reduction in symptoms.
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                Author and article information

                Journal
                Paediatrics & Child Health
                Oxford University Press (OUP)
                1205-7088
                1918-1485
                April 2012
                April 01 2012
                April 2012
                April 01 2012
                : 17
                : 4
                : 193-197
                Article
                10.1093/pch/17.4.193
                3381661
                23543250
                865b2487-d5ea-42dc-bdb6-d09e2abf967c
                © 2012
                History

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