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Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants.

Publication ,  Journal Article
Kishnani, PS; Goldenberg, PC; DeArmey, SL; Heller, J; Benjamin, D; Young, S; Bali, D; Smith, SA; Li, JS; Mandel, H; Koeberl, D; Rosenberg, A ...
Published in: Mol Genet Metab
January 2010

Deficiency of acid alpha glucosidase (GAA) causes Pompe disease, which is usually fatal if onset occurs in infancy. Patients synthesize a non-functional form of GAA or are unable to form native enzyme. Enzyme replacement therapy with recombinant human GAA (rhGAA) prolongs survival in infantile Pompe patients but may be less effective in cross-reactive immunologic material (CRIM)-negative patients. We retrospectively analyzed the influence of CRIM status on outcome in 21 CRIM-positive and 11 CRIM-negative infantile Pompe patients receiving rhGAA. Patients were from the clinical setting and from clinical trials of rhGAA, were 6 months of age, were not invasively ventilated, and were treated with IV rhGAA at a cumulative or total dose of 20 or 40 mg/kg/2 weeks. Outcome measures included survival, invasive ventilator-free survival, cardiac status, gross motor development, development of antibodies to rhGAA, and levels of urinary Glc(4). Following 52 weeks of treatment, 6/11 (54.5%) CRIM-negative and 1/21 (4.8%) CRIM-positive patients were deceased or invasively ventilated (p<0.0001). By age 27.1 months, all CRIM-negative patients and 4/21 (19.0%) CRIM-positive patients were deceased or invasively ventilated. Cardiac function and gross motor development improved significantly more in the CRIM-positive group. IgG antibodies to rhGAA developed earlier and serotiters were higher and more sustained in the CRIM-negative group. CRIM-negative status predicted reduced overall survival and invasive ventilator-free survival and poorer clinical outcomes in infants with Pompe disease treated with rhGAA. The effect of CRIM status on outcome appears to be mediated by antibody responses to the exogenous protein.

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Published In

Mol Genet Metab

DOI

EISSN

1096-7206

Publication Date

January 2010

Volume

99

Issue

1

Start / End Page

26 / 33

Location

United States

Related Subject Headings

  • alpha-Galactosidase
  • Treatment Outcome
  • Retrospective Studies
  • Recombinant Proteins
  • Muscle Strength
  • Male
  • Infant
  • Immunoglobulin G
  • Humans
  • Glycogen Storage Disease Type II
 

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Kishnani, P. S., Goldenberg, P. C., DeArmey, S. L., Heller, J., Benjamin, D., Young, S., … Chen, Y.-T. (2010). Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants. Mol Genet Metab, 99(1), 26–33. https://doi.org/10.1016/j.ymgme.2009.08.003
Kishnani, Priya S., Paula C. Goldenberg, Stephanie L. DeArmey, James Heller, Danny Benjamin, Sarah Young, Deeksha Bali, et al. “Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants.Mol Genet Metab 99, no. 1 (January 2010): 26–33. https://doi.org/10.1016/j.ymgme.2009.08.003.
Kishnani PS, Goldenberg PC, DeArmey SL, Heller J, Benjamin D, Young S, et al. Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants. Mol Genet Metab. 2010 Jan;99(1):26–33.
Kishnani, Priya S., et al. “Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants.Mol Genet Metab, vol. 99, no. 1, Jan. 2010, pp. 26–33. Pubmed, doi:10.1016/j.ymgme.2009.08.003.
Kishnani PS, Goldenberg PC, DeArmey SL, Heller J, Benjamin D, Young S, Bali D, Smith SA, Li JS, Mandel H, Koeberl D, Rosenberg A, Chen Y-T. Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants. Mol Genet Metab. 2010 Jan;99(1):26–33.
Journal cover image

Published In

Mol Genet Metab

DOI

EISSN

1096-7206

Publication Date

January 2010

Volume

99

Issue

1

Start / End Page

26 / 33

Location

United States

Related Subject Headings

  • alpha-Galactosidase
  • Treatment Outcome
  • Retrospective Studies
  • Recombinant Proteins
  • Muscle Strength
  • Male
  • Infant
  • Immunoglobulin G
  • Humans
  • Glycogen Storage Disease Type II