The main risk of providing exogenous protein to compensate for the genetic deficiency of the endogenous protein is the development of neutralizing antibodies, which have been observed in a subset of patients with inherited deficiencies of coagulation proteins (e.g., factors VII, VIII, and IX) [58], ß-glucocerebrosidase factor deficiency underlying Gaucher disease [59], and adenosine deaminase deficiency underlying severe combined immunodeficiency [60]. Here, GBA1 is linked to combined immunodeficiency.