Suggestive evidence of erythropoietin level abnormality in patients with sporadic and familial cases of the restless legs syndrome.

BACKGROUND: The restless legs syndrome (RLS) is divided into two forms: idiopathic and secondary. About half the cases of the former are found to have a positive family history. The lack of objective and quantitative parameters in familial RLS also represents a drawback for genetic studies. We tried to find a feature distinguishing the sporadic from the familial forms of the RLS.

METHODS: RLS patients were examined for clinical picture and laboratory markers including erythropoietin levels. Patients with a priori known causes of secondary RLS, were excluded. All biochemical and hematological parameters were standardized for sex and age groups relative to the population mean and standard deviation.

RESULTS: In our set of 311 patients (65.3% women, mean age 54.6 years, SD 14.7 years) 96 reported positive family history (64.6% women, mean age 53.1 years, SD 15.8 years). We found a significantly lower age at the onset of RLS symptoms in familial cases (mean 29.3 vs. 44.0, Z 5.9, p<0.0001), and, in sporadic cases, a significantly lower absolute count of red blood cells (Z -2.02, p=0.043 respectively). Erythropoietin levels in the familial cases were significantly lower than in the reference population (median -2.26 SDs from the mean). None of the other parameters were significantly different between the groups.

CONCLUSIONS: Our results confirm previously published lower age at symptom onset in familial RLS and provide the first evidence of lower erythropoietin levels in RLS patients. These observations might help to identify the specific phenotype for genetic association studies.