Usefulness of lyso-globotriaosylsphingosine in dried blood spots in the differential diagnosis between multiple sclerosis and Anderson–Fabry's disease

•LysoGb3 is not elevated in patients whith multiple sclerosis.•The cut-off point 3.5 ng/mL, for LysoGb3 in DBS, is valid to rule out Fabry disease.•If demyelinating lesions are present LysoGb3 is enough to discard Fabry disease. The presence of white mater lesions in the central nervous system forces the differential diagnosis between multiple sclerosis (MS) and Anderson–Fabry disease (FD). Due to the type of inheritance, linked to the X chromosome, the diagnosis of FD is especially difficult in women. Tissue´s deposits of globotriaosylceramide (Gb3) are characteristics for FD and the deacylated form of Gb3 (Globotriaosylsphingosine or LysoGb3) is specific for this entity. Our objective is to investigate if concentrations of plasma Lyso-Gb3 are useful for ruling out the FD in a Spanish cohort of patients with a previous diagnosis of MS. we evaluated the α-galactosidase A enzymatic activity in 154 patients with a previous diagnosis of MS (93 women and 61 men): 103 Relapsing Remitting MS patients, 19 progressive MS patients and 32 with the clinically isolated syndrome. 116 (75% of the patients) were on MS disease modifying therapy. Enzymatic assay was completed in all cases and done on dried blood spot (DBS) samples. Subsequently the GLA gene was sequenced only in males and females who presented an enzymatic assay significantly lower than standardized controls (