and Amenability to Migalastat in Fabry Disease.

Migalastat (1-deoxygalactonojirimycin) is approved for the treatment of Fabry disease (FD) in patients with an amenable mutation. Currently, there are at least 367 amenable and 711 non-amenable mutations known, based on an good laboratory practice (GLP) assay. Recent studies demonstrated that amenability of mutations did not necessarily correspond to amenability of migalastat-treated patients. This discrepancy might be due to (methodological) limitations of the current GLP-HEK assay. Currently, there are several published comparable cell-based amenability assays, with partially different outcomes for the same tested mutation, leading to concerns in FD-treating physicians. The aim of this review is to elucidate the idea of amenability assays from their beginning, starting with patient-specific primary cells to high-throughput assays based on overexpression. Consequently, we compare methods of current assays, highlighting their similarities, as well as their pros and cons. Finally, we provide a literature-based list of α-galactosidase A mutations, tested by different assays to provide a comprehensive overview of amenable mutations as a good basis for the decision-making by treating physicians. Since amenability does not always correspond with amenability, the treating clinician has the responsibility to monitor clinical and laboratory features to verify clinical response.