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Mol Genet Metab. 2019 Jul 30. pii: S1096-7192(19)30459-7. doi: 10.1016/j.ymgme.2019.07.016. [Epub ahead of print]

Ten years of enzyme replacement therapy in paediatric onset mucopolysaccharidosis II in England.

Author information

1
Willink Biochemical Genetics Unit, Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester Foundation Trust, Manchester M13 9WL, UK. Electronic address: alexander.broomfield@mft.nhs.uk.
2
Metabolic Medicine Unit, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK.
3
Willink Biochemical Genetics Unit, Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester Foundation Trust, Manchester M13 9WL, UK.
4
Department of Inherited Metabolic Disorders, Birmingham Women's and Children's Hospital Foundation Trust, Steelhouse Lane, Birmingham, UK.
5
Department of Physiotherapy, Royal Manchester Children's Hospital, Manchester Foundation Trust, Manchester M13 9WL, UK.
6
Regional Genetics Laboratories, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
7
Department of Psychology, Royal Manchester Children's Hospital, Manchester Foundation Trust, Manchester M13 9WL, UK.
8
Lysosomal Disorders Unit, Institute of Immunity and Transplantation, Royal Free London NHS Foundation Trust, Pond Street, London NW32QG, UK.

Abstract

The outcome of 110 patients with paediatric onset mucopolysaccharidosis II (MPS II) since the commercial introduction of enzyme replacement therapy (ERT) in England in 2007 is reported. Median length of follow up was 10 years 3 months (range = 1 y 2 m to 18 years 6 month). 78 patients were treated with ERT, 18 had no ERT or disease modifying treatment 7 had haematopoietic stem cell transplant, 4 experimental intrathecal therapy and 3 were lost to follow up. There is clear evidence of improved survival (median age of death of ERT treated (n = 16) = 15.13 years (range = 9.53 to 20.58 y), and untreated (n = 17) = 11.43 y (0.5 to 19.13 y) p = .0005). Early introduction of ERT improved respiratory outcome at 16 years, the median FVC (% predicted) of those in whom ERT initiated <8 years = 69% (range = 34-86%) and 48% (25-108) (p = .045) in those started >8 years. However, ERT appears to have minimal impact on hearing, carpal tunnel syndrome or progression of cardiac valvular disease. Cardiac valvular disease occurred in 18/46 (40%), with progression occurring most frequently in the aortic valve 13/46 (28%). The lack of requirement for neurosurgical intervention in the first 8 years of life suggests that targeted imaging based on clinical symptomology would be safe in this age group after baseline assessments. There is also emerging evidence that the neurological phenotype is more nuanced than the previously recognized dichotomy of severe and attenuated phenotypes in patients presenting in early childhood.

KEYWORDS:

Enzyme replacement therapy (ERT); Hunter syndrome; Idursulfase; Mucopolysaccharidosis II; Paediatric

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