Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy

J Edmond Wraith, Maurizio Scarpa, Michael Beck, Olaf A Bodamer, Linda De Meirleir, Nathalie Guffon, Allan Meldgaard Lund, Gunilla Malm, Ans T Van der Ploeg, Jiri Zeman, J Edmond Wraith, Maurizio Scarpa, Michael Beck, Olaf A Bodamer, Linda De Meirleir, Nathalie Guffon, Allan Meldgaard Lund, Gunilla Malm, Ans T Van der Ploeg, Jiri Zeman

Abstract

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate-2-sulphatase, leading to progressive accumulation of glycosaminoglycans in nearly all cell types, tissues and organs. Clinical manifestations include severe airway obstruction, skeletal deformities, cardiomyopathy and, in most patients, neurological decline. Death usually occurs in the second decade of life, although some patients with less severe disease have survived into their fifth or sixth decade. Until recently, there has been no effective therapy for MPS II, and care has been palliative. Enzyme replacement therapy (ERT) with recombinant human iduronate-2-sulphatase (idursulfase), however, has now been introduced. Weekly intravenous infusions of idursulfase have been shown to improve many of the signs and symptoms and overall wellbeing in patients with MPS II. This paper provides an overview of the clinical manifestations, diagnosis and symptomatic management of patients with MPS II and provides recommendations for the use of ERT. The issue of treating very young patients and those with CNS involvement is also discussed. ERT with idursulfase has the potential to benefit many patients with MPS II, especially if started early in the course of the disease.

Figures

Fig. 1
Fig. 1
Appearance of a child with mucopolysaccharidosis type II (Hunter syndrome) at (a) 6 years of age and (b) 12 years of age, illustrating the ‘typical’ clinical phenotype at the more severe end of the disease spectrum. The manifestations of the syndrome and the rate of progression, however, may vary widely among individual patients
Fig. 2
Fig. 2
Reported age at onset and prevalence of clinical features in 82 patients with mucopolysaccharidosis type II (Hunter syndrome) enrolled in HOS, the Hunter Outcome Survey
Fig. 3
Fig. 3
Mortality by age of patients with mucopolysaccharidosis type II (Hunter syndrome) in the UK. Data are from the Society for Mucopolysaccharide Diseases (MPS Society) and are based on patients registered with the MPS Society between 1950 and October 2006

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