The impact of antibodies in late-onset Pompe disease: a case series and literature review

Abstract

Pompe disease (glycogen storage disease type II, GSD II) is an autosomal recessive disease caused by a deficiency of acid α-glucosidase (GAA), leading to lysosomal glycogen accumulation in various tissues, most notably cardiac, skeletal and smooth muscle. While both infantile and late-onset patients have benefited greatly from alglucosidase alfa (Myozyme®) enzyme replacement therapy (ERT), a subgroup of patients does not demonstrate as pronounced a response as others. Various factors have been identified which may help predict the response to ERT in infantile Pompe disease patients. High, sustained antibody titers (HSAT) have been correlated with poor response to ERT in infantile Pompe cases. However, the literature on the role of antibodies in the late-onset Pompe disease (LOPD) population is limited. Our literature review highlights the need for studies to explore the potential impact of antibodies in LOPD. Further supporting the importance of this issue, our retrospective chart review of sixty LOPD patients revealed that six of these sixty (10%) LOPD patients developed HSAT of ≥1:51,200 on two or more occasions at or beyond 6 months on ERT. Here, we present a series of three of these six LOPD patients for whom detailed antibody data and clinical data were available for greater than 1 year on ERT. These three patients developed HSAT corresponding with clinical decline as demonstrated by pulmonary function, quality of life, and motor function testing, affirming the development of HSAT in a subset of patients with LOPD, and its potentially negative impact on clinical response to ERT. The findings of our study and literature review lead us to conclude that there is a strong indication for systematic studies to accurately delineate the potential impact of antibodies in LOPD.