Lymphocytes from patients with Restless Legs Syndrome reflect a protein profile of iron deficiency and hypoxia.

Restless Legs Syndrome (RLS) is a sensory motor disorder that is thought to affect 5-10% of the population. Symptoms include an urge to move the extremities, usually the legs, often accompanied by uncomfortable dysesthesias or paresthesias, which occur primarily during the evening hours. Recent autopsy evidence suggests that iron homeostasis in the brain is altered in RLS. This dysregulation has been linked to the iron regulatory proteins (IRPs), specifically IRP1. The objective of this study was to examine if a peripheral lymphocytes reflect the iron protein profile abnormalities that were observed in the autopsy brain studies of RLS patients. RLS lymphocytes reflect an iron-depleted protein profile (decreased H-ferritin, and increased transferrin, transferrin receptor, and divalent metal transporter 1) relative to the controls. Ferroportin, which transports iron from the cell, is also increased, a finding which is counterintuitive to intracellular iron insufficiency. Hypoxia was explored as a mechanism to explain these divergent results. RLS primary lymphocytes were found to have increased nuclear hypoxia inducible factor (HIF)-1α activity as well as increased erythropoietin (EPO) immunoreactivity. Based on these findings, we conclude that both iron and HIF-1α may have a role in the molecular mechanism of RLS. [ABSTRACT FROM AUTHOR]