Abstract
Mucopolysaccharidosis IVA (MPS IVA) is a degenerative systemic skeletal dysplasia, in which children exhibit marked short stature and become physically handicapped. This study evaluated the growth patterns of patients treated with enzyme replacement therapy (ERT), compared with those of untreated patients. Cross-sectional and longitudinal data of heights and weights were collected from 128 MPS IVA patients and compared with the growth charts of MPS IVA. Twelve patients (six males, six females) starting ERT before 5 years old were treated for at least 2 years. Six out of 12 patients (50%) with ERT over 2 years stopped growing between 94 and 98 cm (mean height of 95.1 ± 2.2 cm) from 5.0 years to 9.0 years of age (mean age of 6.2 ± 1.6 years). The other patients, except one attenuated case, exhibited a marked slow growth velocity from 3.6 years to 7.7 years. Treated and untreated patients with severe phenotype reached their final heights by ~10 years of age. Patients treated with ERT exhibited a reduced pubertal growth spurt analogous to their untreated counterparts, which contributes to the marked short stature associated with MPS IVA. Compared with the growth charts for untreated patients, patients treated with ERT did not show any significant increase in growth in any age group. Overall, ERT-treated patients do not experience growth improvement and continue to exhibit poor growth despite early ERT intervention before 5 years of age. These findings indicate that current intravenous ERT is ineffective at correcting abnormal growth in MPS IVA.
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Acknowledgements
This work was supported by grants from The Carol Ann Foundation, Angelo R. Cali & Mary V. Cali Family Foundation, Inc., The Vain and Harry Fish Foundation, Inc., The Bennett Foundation, Jacob Randall Foundation, Austrian and Japanese MPS societies, and Nemours Funds. R.W.M. and S.T. were supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of National Institutes of Health (NIH) under grant number P30GM114736. The content of the article has not been influenced by the sponsors.
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Doherty, C., Stapleton, M., Piechnik, M. et al. Effect of enzyme replacement therapy on the growth of patients with Morquio A. J Hum Genet 64, 625–635 (2019). https://doi.org/10.1038/s10038-019-0604-6
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DOI: https://doi.org/10.1038/s10038-019-0604-6
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