Original Paper

European Journal of Pediatrics

, Volume 171, Issue 1, pp 181-188

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

The role of enzyme replacement therapy in severe Hunter syndrome—an expert panel consensus

  • Joseph MuenzerAffiliated withDepartment of Pediatrics, CB 7487, Medical School Wing E Room 117, University of North Carolina at Chapel Hill Email author 
  • , Olaf BodamerAffiliated withDivision of Clinical and Translational Genetics, University of Miami Miller School of Medicine
  • , Barbara BurtonAffiliated withChildren’s Memorial Hospital and Northwestern University Feinberg School of Medicine
  • , Lorne ClarkeAffiliated withDepartment of Medical Genetics, University of British Columbia
  • , Gudrun Schulze FrenkingAffiliated withChildren’s Hospital, University of Mainz
  • , Roberto GiuglianiAffiliated withDepartment of Genetics/UFRGS, Medical Genetics Service/HCPA and INAGEMP
  • , Simon JonesAffiliated withWillink Genetic Medicine, Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust, St Mary’s Hospital
  • , Maria Verónica Muñoz RojasAffiliated withMedical Department, Genzyme do Brasil
  • , Maurizio ScarpaAffiliated withDepartment of Pediatrics, University of Padova
    • , Michael BeckAffiliated withChildren’s Hospital, University of Mainz
    • , Paul HarmatzAffiliated withChildren’s Hospital & Research Center Oakland


Intravenous enzyme replacement therapy (ERT) with idursulfase for Hunter syndrome has not been demonstrated to and is not predicted to cross the blood–brain barrier. Nearly all published experience with ERT with idursulfase has therefore been in patients without cognitive impairment (attenuated phenotype). Little formal guidance is available on the issues surrounding ERT in cognitively impaired patients with the severe phenotype. An expert panel was therefore convened to provide guidance on these issues. The clinical experience of the panel with 66 patients suggests that somatic improvements (e.g., reduction in liver volume, increased mobility, and reduction in frequency of respiratory infections) may occur in most severe patients. Cognitive benefits have not been seen. It was agreed that, in general, severe patients are candidates for at least a 6–12-month trial of ERT, excluding patients who are severely neurologically impaired, those in a vegetative state, or those who have a condition that may lead to near-term death. It is imperative that the treating physician discuss the goals of treatment, methods of assessment of response, and criteria for discontinuation of treatment with the family before ERT is initiated. Conclusion: The decision to initiate ERT in severe Hunter syndrome should be made by the physician and parents and must be based on realistic expectations of benefits and risks, with the understanding that ERT may be withdrawn in the absence of demonstrable benefits.


Mucopolysaccharidosis II Hunter syndrome Enzyme replacement therapy Idursulfase Cognitive impairment Severe phenotype