Inconsistent reporting about dosing, dosing regimen, and immunomodulation therapy in Pompe disease

Journal name:
Genetics in Medicine
Published online

To the Editor: In 2001, Genetics in Medicine published an article titled “Recombinant Human Acid α-Glucosidase Enzyme Therapy for Infantile Glycogen Storage Disease Type II: Results of a Phase I/II Clinical Trial.”1 One of the three patients in that publication (“patient 1”) was recently presented anew in a case report by Banugaria et al.2

The data presented in these two publications are mutually inconsistent. Amalfitano et al.1 published in 2001 that “patient 1” received recombinant human acid α-glucosidase (rhGAA) in a twice-weekly dose of 5mg/kg for 14–17 months (63–76 weeks). In contrast, Banugaria et al.2 reported that “patient 1” received rhGAA in a twice-weekly dose of 5mg/kg for only 5 months (22 weeks), followed by a twice-weekly dose of 10mg/kg over the next 8 months (36 weeks), and a five-times-weekly dose of 10mg/kg over the last 4 months (17 months in total). Furthermore, the recent case report by Banugaria et al.2 revealed that “patient 1” was subjected to three rounds of immunomodulation consisting of cyclophosphamide, intravenous immunoglobulin, plasmapheresis, and increased doses of rhGAA (10mg/kg daily for 9 days in a row). According to Banugaria et al.,2 the three rounds of immunomodulation occurred within the first 13 months (60 weeks) of treatment, but were not reported by Amalfitano et al.1

On another occasion, Hunley presented a case to the American College of Medical Genetics 2003 Annual Meeting. A publication followed 1 year later.3 On the basis of the age at start of treatment and the gender of the patient, the case presented by Hunley et al.3 very likely referred to “patient 2” in Amalfitano et al.1 According to Amalfitano et al.,1 “patient 2” received rhGAA in a twice-weekly dose of 5mg/kg for 14–17 months, but according to Hunley et al.3 “patient 2” received rhGAA in a twice-weekly dose of 5mg/kg for only 15 weeks (3.3 months), followed by a twice-weekly dose of 10mg/kg during the next 27 weeks (11 months), and a five-times-weekly dose of 10mg/kg over the last 11 weeks (2.5 months) (17 months in total). Furthermore, Hunley’s case report3 revealed that “patient 2” underwent experimental immune tolerance therapy beginning after 24 weeks (5.3 months) of treatment for 10 days, which consisted of frequent plasmapheresis and intravenous immunoglobulin G administration, with daily infusions of rhGAA (10mg/kg body weight) and cyclophosphamide. As with “patient 1,” none of these interventions were mentioned in the article published in Genetics in Medicine.1


Erasmus MC and its inventors of methods to produce recombinant human acid α-glucosidase for treatment of Pompe disease receive royalties and provide consultancy to Genzyme Corporation (Cambridge, MA) pursuant to an agreement between Genzyme Corporation and Erasmus MC.


  1. Amalfitano A, Bengur AR, Morse RP, et al. Recombinant human acid α-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial. Genet Med 2001;3:132138.
  2. Banugaria SG, Patel TT, Mackey J, et al. Persistence of high sustained antibodies to enzyme replacement therapy despite extensive immunomodulatory therapy in an infant with Pompe disease. Mol Genet Metab 2012;105:677680.
  3. Hunley TE, Corzo D, Dudek M, et al. Nephrotic syndrome complicating α-glucosidase replacement therapy for Pompe disease. Pediatrics 2004;114:e532e535.

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  1. Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands

    • AJJ Reuser

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