Tags

Type your tag names separated by a space and hit enter

An individually, modified approach to desensitize infants and young children with Pompe disease, and significant reactions to alglucosidase alfa infusions.
Mol Genet Metab 2011 Sep-Oct; 104(1-2):118-22MG

Abstract

PURPOSE

Pompe disease (PD) is a progressive metabolic myopathy for which the only available treatment is alglucosidase alfa (Myozyme®). Enzyme replacement therapy (ERT) has improved ventilator-free survival, and cardiac and motor functions in patients with infantile PD. However, for an adequate response to occur, a large amount of enzymes must be infused. In some patients, this may be problematic due to infusion-associated reactions (IARs) occurring in approximately 50% of patients receiving alglucosidase alfa infusions. Whilst the majority of these reactions are mild, life threatening hypersensitivity reactions may occur in some patients. In these patients desensitization is indicated to enable continued ERT safely. Infants and young children with PD and significant infusion reactions pose unique management challenges because of their young age, limited communication skills, variable presentation and underlying cardiomyopathy.

METHODS/SUBJECTS

In 2 patients with PD who experienced significant ERT-related reactions: an infant (IgE positive) and a young child (IgE negative), we implemented a desensitization protocol, that started by administering a reduced dose of alglucosidase alfa (10 mg/kg weekly) instead of the standard (20 mg/kg bi-weekly) using serial micro-dilutions that were individually prepared and delivered in a highly regulated manner based on patients' clinical manifestations and tolerance.

RESULTS

Successful desensitization was achieved in both patients, allowing them to eventually continue to receive the full dose of ERT safely.

CONCLUSION

Therapeutic demands in infants and young children with PD need to be tailored according to the patient presentation, and underlying cardiac and fluid-volume status. Desensitization allowed both patients to continue alglucosidase alfa treatment at the recommended dose without prolonged interruption of therapy, or further reactions.

Authors+Show Affiliations

Department of Pediatrics, Division of Medical Genetics, Duke University Medical, Center, Durham, NC 27710, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21802969

Citation

El-Gharbawy, Areeg H., et al. "An Individually, Modified Approach to Desensitize Infants and Young Children With Pompe Disease, and Significant Reactions to Alglucosidase Alfa Infusions." Molecular Genetics and Metabolism, vol. 104, no. 1-2, 2011, pp. 118-22.
El-Gharbawy AH, Mackey J, DeArmey S, et al. An individually, modified approach to desensitize infants and young children with Pompe disease, and significant reactions to alglucosidase alfa infusions. Mol Genet Metab. 2011;104(1-2):118-22.
El-Gharbawy, A. H., Mackey, J., DeArmey, S., Westby, G., Grinnell, S. G., Malovrh, P., ... Kishnani, P. S. (2011). An individually, modified approach to desensitize infants and young children with Pompe disease, and significant reactions to alglucosidase alfa infusions. Molecular Genetics and Metabolism, 104(1-2), pp. 118-22. doi:10.1016/j.ymgme.2011.07.004.
El-Gharbawy AH, et al. An Individually, Modified Approach to Desensitize Infants and Young Children With Pompe Disease, and Significant Reactions to Alglucosidase Alfa Infusions. Mol Genet Metab. 2011;104(1-2):118-22. PubMed PMID: 21802969.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An individually, modified approach to desensitize infants and young children with Pompe disease, and significant reactions to alglucosidase alfa infusions. AU - El-Gharbawy,Areeg H, AU - Mackey,Joanne, AU - DeArmey,Stephanie, AU - Westby,Greg, AU - Grinnell,Sherry G, AU - Malovrh,Peggy, AU - Conway,Robert, AU - Kishnani,Priya S, Y1 - 2011/07/13/ PY - 2011/05/24/received PY - 2011/07/04/revised PY - 2011/07/04/accepted PY - 2011/8/2/entrez PY - 2011/8/2/pubmed PY - 2012/1/10/medline SP - 118 EP - 22 JF - Molecular genetics and metabolism JO - Mol. Genet. Metab. VL - 104 IS - 1-2 N2 - PURPOSE: Pompe disease (PD) is a progressive metabolic myopathy for which the only available treatment is alglucosidase alfa (Myozyme®). Enzyme replacement therapy (ERT) has improved ventilator-free survival, and cardiac and motor functions in patients with infantile PD. However, for an adequate response to occur, a large amount of enzymes must be infused. In some patients, this may be problematic due to infusion-associated reactions (IARs) occurring in approximately 50% of patients receiving alglucosidase alfa infusions. Whilst the majority of these reactions are mild, life threatening hypersensitivity reactions may occur in some patients. In these patients desensitization is indicated to enable continued ERT safely. Infants and young children with PD and significant infusion reactions pose unique management challenges because of their young age, limited communication skills, variable presentation and underlying cardiomyopathy. METHODS/SUBJECTS: In 2 patients with PD who experienced significant ERT-related reactions: an infant (IgE positive) and a young child (IgE negative), we implemented a desensitization protocol, that started by administering a reduced dose of alglucosidase alfa (10 mg/kg weekly) instead of the standard (20 mg/kg bi-weekly) using serial micro-dilutions that were individually prepared and delivered in a highly regulated manner based on patients' clinical manifestations and tolerance. RESULTS: Successful desensitization was achieved in both patients, allowing them to eventually continue to receive the full dose of ERT safely. CONCLUSION: Therapeutic demands in infants and young children with PD need to be tailored according to the patient presentation, and underlying cardiac and fluid-volume status. Desensitization allowed both patients to continue alglucosidase alfa treatment at the recommended dose without prolonged interruption of therapy, or further reactions. SN - 1096-7206 UR - https://www.unboundmedicine.com/medline/citation/21802969/An_individually_modified_approach_to_desensitize_infants_and_young_children_with_Pompe_disease_and_significant_reactions_to_alglucosidase_alfa_infusions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(11)00217-4 DB - PRIME DP - Unbound Medicine ER -