The effect of idursulfase on growth in patients with Hunter Syndrome: data from the Hunter Outcome Survey (HOS)

TY - JOUR

T1 - The effect of idursulfase on growth in patients with Hunter Syndrome: data from the Hunter Outcome Survey (HOS)

AU - Jones, Simon A

AU - Parini, Rossella

AU - Harmatz, Paul

AU - Giugliani, Roberto

AU - Fang, Juanzhi

AU - Mendelsohn, Nancy J

AU - HOS Natural History Working Group on behalf of HOS Investigators

AU - Muschol, Nicole Maria

N1 - Copyright © 2013 Elsevier Inc. All rights reserved.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - Hunter syndrome (mucopolysaccharidosis type II) is a rare and life-limiting multisystemic disorder with an X-linked recessive pattern of inheritance. Short stature is a prominent feature of this condition. This analysis aimed to investigate the effects of enzyme replacement therapy with idursulfase on growth in patients enrolled in HOS - the Hunter Outcome Survey which is a multinational observational database. As of Jan 2012, height data before treatment were available for 567 of 740 males followed prospectively after HOS entry. Cross-sectional analysis showed that short stature became apparent after approximately 8 years of age; before this, height remained within the normal range. Age-corrected standardized height scores (z-scores) before and after treatment were assessed using piecewise regression model analysis in 133 patients (8-15 years of age at treatment start; data available on ≥ 1 occasion within +/-24 months of treatment start; growth hormone-treated patients excluded). Results showed that the slope after treatment (slope=-0.005) was significantly improved compared with before treatment (slope=-0.043) (difference=0.038, p=0.004). Analysis of covariates (age at treatment start, cognitive involvement, presence of puberty at the start of ERT, mutation type, functional classification), showed a significant influence on growth of mutation type (height deficit in terms of z-scores most pronounced in patients with deletions/large rearrangements/nonsense mutations, p<0.0001) and age (most pronounced in the 12-15-year group, p<0.0001). Cognitive involvement, pubertal status at the start of ERT and functional classification were not related to the growth deficit or response to treatment. In conclusion, the data showed an improvement in growth rate in patients with Hunter syndrome following idursulfase treatment.

AB - Hunter syndrome (mucopolysaccharidosis type II) is a rare and life-limiting multisystemic disorder with an X-linked recessive pattern of inheritance. Short stature is a prominent feature of this condition. This analysis aimed to investigate the effects of enzyme replacement therapy with idursulfase on growth in patients enrolled in HOS - the Hunter Outcome Survey which is a multinational observational database. As of Jan 2012, height data before treatment were available for 567 of 740 males followed prospectively after HOS entry. Cross-sectional analysis showed that short stature became apparent after approximately 8 years of age; before this, height remained within the normal range. Age-corrected standardized height scores (z-scores) before and after treatment were assessed using piecewise regression model analysis in 133 patients (8-15 years of age at treatment start; data available on ≥ 1 occasion within +/-24 months of treatment start; growth hormone-treated patients excluded). Results showed that the slope after treatment (slope=-0.005) was significantly improved compared with before treatment (slope=-0.043) (difference=0.038, p=0.004). Analysis of covariates (age at treatment start, cognitive involvement, presence of puberty at the start of ERT, mutation type, functional classification), showed a significant influence on growth of mutation type (height deficit in terms of z-scores most pronounced in patients with deletions/large rearrangements/nonsense mutations, p<0.0001) and age (most pronounced in the 12-15-year group, p<0.0001). Cognitive involvement, pubertal status at the start of ERT and functional classification were not related to the growth deficit or response to treatment. In conclusion, the data showed an improvement in growth rate in patients with Hunter syndrome following idursulfase treatment.

KW - Adolescent

KW - Adult

KW - Child

KW - Codon, Nonsense

KW - Data Collection

KW - Databases, Factual

KW - Dwarfism

KW - Female

KW - Genes, Recessive

KW - Genes, X-Linked

KW - Growth Hormone

KW - Humans

KW - Iduronate Sulfatase

KW - Male

KW - Mucopolysaccharidosis II

U2 - 10.1016/j.ymgme.2013.03.001

DO - 10.1016/j.ymgme.2013.03.001

M3 - SCORING: Journal article

C2 - 23537841

VL - 109

SP - 41

EP - 48

JO - MOL GENET METAB

JF - MOL GENET METAB

SN - 1096-7192

IS - 1

ER -