Abstract
Pompe disease is characterized by deficiency or absence of activity of the lysosomal enzyme acid alpha-glucosidase. As a result of ineffective metabolism, glycogen progressively accumulates in muscle tissues. Patients with an aggressive classic infantile-onset form generally rapidly die of cardiorespiratory failure. A cross-reactive immunological material (CRIM)-negative status is predictive of high anti-alglucosidase alfa antibody titers and usually a poor clinical outcome of enzyme replacement therapy (ERT). CRIM-positive patients can also develop robust antibody titers complicating therapeutic management.
We successfully used an immune modulation therapy (IMT) protocol in a CRIM-positive infantile-onset patient with Pompe disease in whom infusions had to be temporarily discontinued because of safety concerns despite administration of pre-infusion medication. Prior to discontinuation, she had shown signs of clinical deterioration and continuous ventilation support through a tracheostomy was required. She was found to be positive for anti-alglucosidase alfa antibodies (1:6,400). IMT (rituximab, methotrexate and intravenous gamma globulin) was started, ERT was safely reintroduced during the IMT induction phase and, subsequently, the enzyme dose was increased, all without any complications. Antibodies disappeared, IMT was tapered and discontinued, and cadiomyopathy steadily improved. During 1 year of follow-up, she remained ventilator dependent and no gains in motor skills were noticed; motor functions will be closely monitored during sustained ERT.
Although the reversal of clinical decline in our CRIM-positive and antibody-positive infant with Pompe disease cannot be solely attributed to IMT, our experiences with this protocol may be helpful to other physicians encountering comparable therapeutic dilemmas.
Competing interests: None declared.
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Notes
- 1.
Summary of Product Characteristics Myozyme®, http://www.ema.europa.eu/.
Abbreviations
- CRIM:
-
Cross-reactive immunological material
- ERT:
-
Enzyme replacement therapy
- GAA:
-
Acid alpha-glucosidase
- IAR:
-
Infusion-associated reaction
- IMT:
-
Immune modulation therapy
- LVMI:
-
Left ventricular mass index
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Acknowledgment
The authors thank Nancy Mendelsohn, M.D., and Yoav Messinger, M.D., from Children’s Hospitals and Clinics of Minnesota for developing the IMT regimen and providing it to us.
Furthermore, the authors acknowledge the editorial support of Hans Ebels, M.D., from Genzyme Europe. The authors maintained full and independent responsibility for the content of this manuscript.
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Communicated by: Robert Steiner
Synopsis
Synopsis
Immune tolerance induction is a viable therapeutic option in poorly responding infantile, antibody-positive patients with Pompe disease.
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Markic, J. et al. (2011). Immune Modulation Therapy in a CRIM-Positive and IgG Antibody-Positive Infant with Pompe Disease Treated with Alglucosidase Alfa: A Case Report. In: JIMD Reports - Case and Research Reports, 2011/2. JIMD Reports, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_34
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DOI: https://doi.org/10.1007/8904_2011_34
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