The Role of Iron in Pediatric Restless Legs Syndrome and Periodic Limb Movements in Sleep

Abstract

Restless legs syndrome (RLS) is a common and treatable neurologic condition in pediatric patients, with a prevalence as high as 2 to 3%. The diagnosis of RLS is made clinically based on an urge to move the legs accompanied by lower extremity discomfort that occurs during rest usually later in the day and is relieved by movement. Periodic limb movements in sleep (PLMS) can overlap with RLS, although PLMS also exists as a separate entity characterized by stereotyped movements of lower extremities in sleep. Both conditions may be highly debilitating and interfere with daily function notably in the areas of educational attainment and behavioral regulation. Iron deficiency has been implicated in the pathophysiology of both RLS and PLMS. Current evidence suggests that treatment of ferritin levels < 50 µg/L may be beneficial in improving pediatric RLS symptoms and comorbid conditions or daytime dysfunction associated with RLS. Areas for future research include (1) clarifying the ferritin or other iron status measure level which predicts iron treatment will provide symptom improvement in pediatric patients, and (2) randomized clinical trials using iron therapy to determine the degree and duration of treatment.

Sleeping without Prescription: Management of Sleep Disorders in Children with Autism with Non-Pharmacological Interventions and Over-the-Counter Treatments

“…Nevertheless, many authors suggest the administration of iron supplements in this population when low ferritin levels (below 30–50 ng/mL) and poor sleep quality are both present [ 20 , 25 , 164 ]. The recommended initial dose in the pediatric age is usually 1–2 mg/kg/day of elemental iron divided in 2–3 doses between meals; the clinician may then titrate up to 6 mg/kg/day, in order to reach a serum ferritin concentration of 30–50 ng/mL or more [ 20 , 173 ]. Follow-up visits should be scheduled within 2–3 months of oral iron initiation, to check ferritin levels and to identify potential hinders to iron absorption and adherence to therapy [ 167 ].…”

Restless Sleep Disorder and the Role of Iron in Other Sleep-Related Movement Disorders and ADHD

“…Following absorption into the enterocyte, transport and oxidase proteins mediate iron transfer into the blood. Transferrin is the main iron transporter protein, which provides iron storage in the liver and red cell synthesis in the marrow [56].…”

“…Approximately three months or more of iron treatment are needed to obtain an improvement of symptoms [86][87][88]. Several studies have proven the benefit of iron therapy in decreasing the PLMS index and reducing RLS symptoms in children [56], as well as in adults, at 3-6 months follow-up [35]. For children and adolescents, oral iron therapy has been shown to improve RLS symptoms in several case series [89][90][91].…”