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

To determine if Angelman syndrome patients with sleep complaints have an increased risk of iron deficiency, and if iron therapy improves their sleep difficulties.

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.

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.

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.

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.