The natural history of growth in patients with Hunter syndrome: Data from the Hunter Outcome Survey (HOS).

ABSTRACT

Hunter syndrome (mucopolysaccharidosis type II) affects growth but the overall impact is poorly understood. This study investigated the natural history of growth and related parameters and their relationship with disease severity (as indicated by cognitive impairment). Natural history data from males followed prospectively in the Hunter Outcome Survey registry and not receiving growth hormone or enzyme replacement therapy, or before treatment start, were analysed (N=676; January 2014). Analysis of first-reported measurements showed short stature by 8years of age; median age-corrected standardized height score (z-score) in patients aged 8-12years was -3.1 (1st, 3rd quartile -4.3, -1.7; n=68). Analysis of growth velocity using consecutive values found no pubertal growth spurt. Patients had large head circumference at all ages, and above average body weight and body mass index (BMI) during early childhood (median z-score in patients aged 2-4years, weight [n=271] 1.7 [0.9, 2.4]; BMI [n=249] 2.0 [1.1, 2.7]). Analysis of repeated measurements over time found greater BMI in those with cognitive impairment than those without, but no difference in height, weight or head circumference. Logistic regression modelling (data from all time points) found that increased BMI was associated with the presence of cognitive impairment (odds ratio [95% CI], 3.329 [2.313-4.791]), as were increased weight (2.365 [1.630-3.433]) and head circumference (1.749 [1.195-2.562]), but not reduced height. Unlike some other MPS disorders, there is no evidence at present for predicting disease severity in patients with Hunter syndrome based on changes in growth characteristics.