Clinical trials have demonstrated beneficial effects of enzyme replacement therapy (ERT) with alglucosidase alfa in infants, children and adults with Pompe disease. Recent studies have shown that high antibody titers can occur in patients receiving ERT and counteract the effect of treatment. This particularly occurs in those patients with classic-infantile Pompe disease that do not produce any endogenous acid α-glucosidase (CRIM-negative). It is still unclear to what extent antibody formation affects the outcome of ERT in adults with residual enzyme activity.We present the case of a patient with adult-onset Pompe disease. He was diagnosed at the age of 39. years by enzymatic testing (10.7% residual activity in fibroblasts) and DNA analysis (genotype: c.-32-13T>G/p.Trp516X). Infusion-associated reactions occurred during ERT and the patient's disease progressed. Concurrently, the antibody titer rose to a similarly high level as reported for some CRIM-negative patients with classic-infantile Pompe disease.Using newly developed immunologic-assays we could calculate that approximately 40% of the administered alglucosidase alfa was captured by circulating antibodies. Further, we could demonstrate that uptake of alglucosidase alfa by cultured fibroblasts was inhibited by admixture of the patient's serum.This case demonstrates that also patients with an appreciable amount of properly folded and catalytically active endogenous acid α-glucosidase can develop antibodies against alglucosidase alfa that affect the response to ERT.

, , , , , ,,
Molecular Genetics and Metabolism
Erasmus MC: University Medical Center Rotterdam

de Vries, J.M, van der Beek, N.A.M.E, Kroos, M.A, Ozkan, L, van Doorn, P.A, & Richards, S.M. (2010). High antibody titer in an adult with Pompe disease affects treatment with alglucosidase alfa. Molecular Genetics and Metabolism, 101(4), 338–345. doi:10.1016/j.ymgme.2010.08.009