A new strategy of desensitization in mucopolysaccharidosis type II disease treated with idursulfase therapy: A case report and review of the literature

Vincenza Gragnaniello; Silvia Carraro; Laura Rubert; Daniela Gueraldi; Chiara Cazzorla; Pamela Massa; Stefania Zanconato; Alberto B Burlina

doi:10.1016/j.ymgmr.2022.100878

A new strategy of desensitization in mucopolysaccharidosis type II disease treated with idursulfase therapy: A case report and review of the literature

Mol Genet Metab Rep. 2022 May 5:31:100878. doi: 10.1016/j.ymgmr.2022.100878. eCollection 2022 Jun.

Authors

Vincenza Gragnaniello¹, Silvia Carraro², Laura Rubert¹, Daniela Gueraldi¹, Chiara Cazzorla¹, Pamela Massa¹, Stefania Zanconato², Alberto B Burlina¹

Affiliations

¹ Division of Inherited Metabolic Diseases, Department of Diagnostic Services, University Hospital, Padua, Italy.
² Women's and Children's Health Department, Padua University Hospital, Padua, Italy.

Abstract

Mucopolysaccharidosis type II (MPS II) is a multisystemic lysosomal storage disorder caused by deficiency of the iduronate 2-sulfatase enzyme. Currently, enzyme replacement therapy (ERT) with recombinant idursulfase is the main treatment available to decrease morbidity and improve quality of life. However, infusion-associated reactions (IARs) are reported and may limit access to treatment. When premedication or infusion rate reductions are ineffective for preventing IARs, desensitization can be applied. To date, only two MPS II patients are reported to have undergone desensitization. We report a pediatric patient with recurrent IARs during infusion successfully managed with gradual desensitization. Our protocol started at 50% of the standard dosage infused at concentrations from 0.0006 to 0.06 mg/ml on weeks 1 and 2, followed by 75% of the standard dosage infused at concentrations from 0.0009 to 0.09 mg/ml on weeks 3 and 4, and full standard dosage thereafter, infused at progressively increasing concentrations until the standard infusion conditions were reached at 3 months. Our experience can be used in the management of MPS II patients presenting IARs to idursulfase infusion, even when general preventive measures are already administered.

Keywords: DS, dermatan sulfate; Desensitization; ERT, enzyme replacement therapy; Enzyme replacement therapy; GAGs, glycosaminoglycans; HS, heparan sulfate; HSCT, hematopoietic stem cell transplantation; Hunter disease; I2S, iduronate 2-sulfatase enzyme; IARs, infusion-associated reactions; IDS, iduronate 2-sulfatase gene; Idursulfase; IgE, immunoglobulin E; IgG, immunoglobulin G; Infusion-associated reactions; MPS II, mucopolysaccharidosis type II; MRI, magnetic resonance imaging; MS/MS spectrometry, tandem mass spectrometry; Mucopolysaccharidosis type II; SPTs, skin prick tests.