Figure 1. An algorithm for the management of cross-reactive immunologic material (CRIM)-negative (CN) infantile Pompe disease patients.

^*Institutional review board (IRB) approved study (NCT01665326; www.clinicaltrials.gov) for rapid determination of CRIM status and long-term follow-up of response to treatment and ITI in Pompe disease. ^†CN status determination from an established CRIM negative mutation database, which allows prediction of CN status in more than 90% cases [15]. ^‡ITI regimen is shown in Figure 2. ^§Based on the literature antibody titers sustained at ≥6,400 results in a suboptimal therapeutic response to ERT. For that reason, 6,400 was used a cutoff for further intervention [9], [19]. **Based on the half-life of rituximab, CD19% recovery is typically noted around 5 months. ^††The decision to repeat the same ITI regimen (figure 3) or to administer ITI with a plasma-cell-targeting agent [20] should be based on multiple factors including, but not limited to, patients clinical status, CD19% and Fc_γ receptor polymorphism. ^‡‡ITI regimen with plasma cell targeting agent such as bortezomib has been described previously [20].