Restless legs syndrome in a patient with dysmetabolic iron overload syndrome and abnormal iron deposits in basal ganglia and susbtantia nigra

Introduction Restless Legs Syndrome (RLS) is a sensorimotor disorder involving primarily leg discomfort and motor restlessness. Iron deficiency anemia occurs in secondary cases and a decreased brain iron status in CSF and decreased regional iron particularly in the substantia nigra has been postulated. Materials and methods A 50 years old patient was referred for severe RLS and periodic leg movements (PLM) while sleeping. Past medical history showed completed bladder cancer remission, overweight, high blood pressure and dyslipidemia. Results Neurological examination and standard EEG were normal. The Epworth Sleepiness Scale score was 18. Polysomnography showed a disturbed and fragmented sleep with a reduction in total sleep time, low sleep efficiency, mild OSA with an apnea-hypopnea index of 14,4/h and periodic leg movements index 37,2/h. The serum ferritin was 390  μ g/L, serum iron 175  μ g/dl, transferrin 189 mg/dl, and transferrin saturation index 73%. The genetic study revealed hereterozygosity for the H63D mutation of HFE gen and another mutation in the 5UTR region of HFE gen, both not identified as pathological. The cranial MRI initially normal, showed two years later to RLS diagnosis abnormal iron deposits in globus pallidus, dentate, red nuclei and substantia nigra. Liver MRI showed mild iron overload. The diagnosis was dysmetabolic iron overload syndrome. Conclusion RLS with PLM was associated with high serum ferritin and iron levels, low transferrin and high saturation transferrin index suggesting an impaired mechanism of mobilization of stored iron. The abnormal iron deposits in basal ganglia and substantia nigra revealed a complex disorder of iron central metabolism.