Current recommendations for Fabry disease include α-galactosidase A (AGAL) activity measurements to assess the biochemical response in migalastat-treated patients. Owing to contradictory data from laboratories, we aimed to analyze why AGAL activity measures from dried blood spots (DBS) often fail to detect migalastat-mediated enzymatic activity increases in treated patients.

The optimal time for enzymatic AGAL activity measurement in migalastat-treated patients appears to be 24 h after the last migalastat intake. Since migalastat is a competitive inhibitor of AGAL, enzymatic AGAL activity measurements should be better performed from PBMCs to reduce migalastat-mediated interferences.

43 patients with 58 visits under migalastat were consecutively recruited. Enzymatic AGAL activities were measured from DBS and peripheral blood mononuclear cells (PBMCs). Migalastat concentrations in sera were determined using modified serum-mediated inhibition assays to assess Cmax and serum half-life.

DBS-based AGAL activity measurements of 21 (42.0%) amenable patients were below the limit of detection. Serum samples from migalastat-treated patients showed significant AGAL inhibition, depending on the time between migalastat intake and blood sampling (r2 = 0.8140, p < 0.0001). Migalastat concentrations were determined in serum samples confirming a Cmax at 3 h and a serum half-life of 4 h. At 24 h after intake, migalastat clearance was significantly associated with renal function (r2 = 0.3135, p = 0.0102). Enzymatic AGAL activities were higher in samples from DBS and PBMCs 24 h after migalastat intake (both p < 0.05).