PURPOSE: Fabry disease is an X-linked lysosomal storage disorder caused by 
mutations in the α-galactosidase A gene. Migalastat, a pharmacological 
chaperone, binds to specific mutant forms of α-galactosidase A to restore 
lysosomal activity.
METHODS: A pharmacogenetic assay was used to identify the α-galactosidase A 
mutant forms amenable to migalastat. Six hundred Fabry disease-causing mutations 
were expressed in HEK-293 (HEK) cells; increases in α-galactosidase A activity 
were measured by a good laboratory practice (GLP)-validated assay (GLP 
HEK/Migalastat Amenability Assay). The predictive value of the assay was 
assessed based on pharmacodynamic responses to migalastat in phase II and III 
clinical studies.
RESULTS: Comparison of the GLP HEK assay results in in vivo white blood cell 
α-galactosidase A responses to migalastat in male patients showed high 
sensitivity, specificity, and positive and negative predictive values (≥0.875). 
GLP HEK assay results were also predictive of decreases in kidney 
globotriaosylceramide in males and plasma globotriaosylsphingosine in males and 
females. The clinical study subset of amenable mutations (n = 51) was 
representative of all 268 amenable mutations identified by the GLP HEK assay.
CONCLUSION: The GLP HEK assay is a clinically validated method of identifying 
male and female Fabry patients for treatment with migalastat.Genet Med 19 4, 
430-438.