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


CONCLUSIONS
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and parents and must be based on realistic expectations of benefits and risks, with the understanding that ERT may be withdrawn in the absence of demonstrable benefits.
Department of Pediatrics, University of North Carolina, Chapel Hill, NC 27599-7487, USA. muenzer@med.unc.edu
Joseph
J
Muenzer
Olaf
O
Bodamer
Barbara
B
Burton
Lorne
L
Clarke
Gudrun Schulze
GS
Frenking
Roberto
R
Giugliani
Simon
S
Jones
Maria Verónica Muñoz
MV
Rojas
Maurizio
M
Scarpa
Michael
M
Beck
Paul
P
Harmatz
D018450:Disease Progression; D056947:Enzyme Replacement Therapy; D006801:Humans; D007066:Iduronate Sulfatase / Q000627:therapeutic use*; D016532:Mucopolysaccharidosis II / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D017410:Practice Guidelines as Topic; D016896:Treatment Outcome
D007066:Iduronate Sulfatase; C517982:idursulfase