Abstract:
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.
