The effect of galsulfase enzyme replacement therapy on the growth of patients with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)

Mucopolysaccharidosis (MPS) VI is an autosomal recessive lysosomal storage disorder arising from deficient activity of N-acetylgalactosamine-4-sulfatase (arylsulfatase B) and subsequent intracellular accumulation of the glycosaminoglycans (GAGs) dermatan sulfate and chondroitin-4-sulfate. Manifestations are multi-systemic and include skeletal abnormalities such as dysostosis multiplex and short stature. Reference height-for-age growth charts for treatment-naïve MPS VI patients have been published for both the slowly and rapidly progressing populations. Categorization of disease progression for these charts was based on urinary GAG (uGAG) level; high (N200 μg/mg creatinine) levels identified subjects as rapidly progressing. Height data for 141 patients who began galsulfase treatment by the age of 18 years were collected and stratified by baseline uGAG level and age at ERT initiation in 3-year increments. The referenceMPS VI growth charts were used to calculate change in Z-score from pre-treatment baseline to last follow-up. Among patientswith high baseline uGAG levels, galsulfase ERTwas associatedwith an increase in Z-score for those beginning treatment at 0–3, N3–6, N6– 9, N9–12, and N12–15 years of age (p b 0.05). Increases in Z-score were not detected for patientswho began treatment between 15 and 18 years of age, nor for patients with low (≤200 μg/mg creatinine) baseline uGAG levels, regardless of age at treatment initiation. The largest positive deviation from untreated reference populations was seen in the high uGAG excretion groups who began treatment by 6 years of age, suggesting an age- and severity- dependent impact of galsulfase ERT on growth.BioMarin Pharmaceutical Inc. and was supported in part by UK MRC through grant number MR/M012069/1 (Dr. Cole) and the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through UCSF-CTSI grant number UL1 TR000004 (Dr. Harmatz). Remove selectedhttp://www.elsevier.com/locate/ymgmeam2017Immunolog