Iron Deficiency and Its Role in Sleep Disruption in Patients With Angelman Syndrome

Objective: To determine if Angelman syndrome patients with sleep complaints have an increased risk of iron deficiency, and if iron therapy improves their sleep difficulties. Background: About two-thirds of Angelman syndrome patients experience sleep difficulties, which are likely multifactorial. Because iron deficiency can contribute toward restlessness in sleep, we investigated whether it might be a contributing factor in this special population. Methods: This retrospective study involved medical record review of Angelman syndrome patients <18 years old who had attended our multidisciplinary Angelman syndrome clinic and had sleep complaints. Serum ferritin levels were compared to age- and sex-matched controls. Sleep history and nocturnal polysomnogram findings of the Angelman syndrome patients were also characterized. Results: Nineteen Angelman syndrome patients (9 female, mean age 6.2±4.4 years) were identified. All 19 reported sleep difficulties. The mean serum ferritin level was 19.9±8.5 μg/L, while that in controls was 27.8±17.8 μg/L (P value.13). The odds ratio of iron deficiency in Angelman syndrome compared to controls was 4.17 (95% confidence interval 1.23-14.10), using normal serum ferritin level of 24 μg/L based on literature. Fifteen Angelman syndrome patients underwent nocturnal polysomnogram with 9/15 showing an elevated periodic limb movement index (overall mean 9.8±10.4). Seventeen of 19 received iron therapy. Twelve had follow-up after iron therapy, with parents reporting improved sleep quality. Eight had serum ferritin levels rechecked after iron therapy, showing a mean increase of 24±5.1 μg/L. Conclusions: Sleep difficulties in Angelman syndrome, though multifactorial, may in part be related to iron deficiency. Treatment with iron improved sleep to a modest degree in this population.