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

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 (>200μg/mg creatinine) levels identified subjects as rapidly progressing. Height data for 141 patients who began galsulfase treatment by the age of 18years were collected and stratified by baseline uGAG level and age at ERT initiation in 3-year increments. The reference MPS VI growth charts were used to calculate change in Z-score from pre-treatment baseline to last follow-up. Among patients with high baseline uGAG levels, galsulfase ERT was associated with an increase in Z-score for those beginning treatment at 0-3, >3-6, >6-9, >9-12, and >12-15years of age (p<0.05). Increases in Z-score were not detected for patients who began treatment between 15 and 18years of age, nor for patients with low (≤200μg/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 6years of age, suggesting an age- and severity-dependent impact of galsulfase ERT on growth.

Enzyme replacement therapy outcomes across the disease spectrum: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program

“…No conclusions can be made regarding the impact of ERT on growth due to limited availability of growth data before treatment initiation. However, a recent study including data from the galsulfase clinical trials, the CSP, and the Resurvey Study demonstrated increases in height z‐score in patients with high uGAG (>200 μg/mg creatinine) only, and up to 15 years of age . The greatest improvements were seen when ERT was initiated before 6 years of age.…”

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

“…The effect of ERT on growth on the long term has been studied in MPS I, MPS II, MPS IVA, MPS VI [37,45,47,70,[101][102][103][104][105][106][107]. Many studies report limited improvement of growth after starting ERT [37,45,70,[101][102][103][104]. A few long-term studies did not find any efficacy of ERT on growth, even when started at a young age [40,[105][106][107].…”

“…In general, some studies show a limited effect of ERT on growth in patients who had started treatment before puberty or at least below 15 years [37,45,70,[101][102][103][104]. Furthermore, patients showing a growth delay before commencing ERT, did not obtain a tangible improvement [101][102][103][104].…”

The use of port-a-caths in adult patients with Lysosomal Storage Disorders receiving Enzyme Replacement Therapy-one centre experience

“…The clinical presentation is multi-systemic. LSDs affect different parts of the body, including the musculoskeletal system, central nervous system, skin, heart and kidneys [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] . Patients affected by these conditions often require recurrent courses of Enzyme Replacement Therapy (ERT) [12] .…”

“…Patients affected by these conditions often require recurrent courses of Enzyme Replacement Therapy (ERT) [12] . ERTs are now available for several LSDs such as Gaucher disease [13] , Pompe disease [14] , Fabry disease [15] , MPS I [16] , MPS II [17] , MPS IV [18] , MPS VI [19] and potentially for MPS VII soon. The key to success of the therapy is an early onset of treatment.…”