Is it Fabry disease?

Fabry disease is caused by mutations in the GLA gene that lower α-galactosidase A activity to less than 25-30% of the mean normal level. Several GLA variants have been identified that are associated with relatively elevated residual α-galactosidase A. The challenge is to determine which GLA variants can cause clinical manifestations related to Fabry disease. Here, we review the various types of GLA variants and recommend that pathogenicity be considered only when associated with elevated globotriaosylceramide in disease-relevant organs and tissues as analyzed by mass spectrometry. This criterion is necessary to ensure that very costly and specific therapy is provided only when appropriate.Genet Med 18 12, 1181-1185.