Background: The skeletal phenotype of mucopolysaccharidosis VI (MPS VI) is characterized by short stature and growth failure.Objective: The purpose of this study was to construct reference growth curves for MPS VI patients with rapidly and slowly progressive disease.Methods: We pooled cross-sectional and longitudinal height for age data from galsulfase (Naglazyme ® , BioMarin Pharmaceutical Inc.), treatment naïve patients (n ¼ 269) who participated in various MPS VI studies, including galsulfase clinical trials and their extension programs, the MPS VI clinical surveillance program (CSP), and the MPS VI survey and resurvey studies, to construct growth charts for the MPS VI population. There were 229 patients included in this study, of which data from 207 patients 25 years of age with 513 height measurements were used for constructing reference growth curves.Results: Height for age growth curves for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles were constructed for patients with rapidly and slowly progressing disease defined by the pre-enzyme replacement therapy (ERT) uGAG levels of > or 200 mg/mg creatinine. The mean (SD) pre-ERT uGAG levels were 481.0 (218.6) and 97.8 (56.3) mg/mg creatinine for the patients 25 years of age with rapidly (n ¼ 131) and slowly (n ¼ 76) progressing MPS VI disease, respectively. The median growth curves for patients with and >200 mg/mg creatinine were above and below the median (50th percentile) growth curve for the entire MPS VI population.Conclusion: MPS VI growth charts have been developed to assist in the clinical management of MPS VI patients.

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.

Background Despite being recognized as the gold standard in isolated clubfoot treatment, the Ponseti casting method has yielded variable results. Few studies have directly compared common predictors of treatment failure between institutions with high versus low failure rates.

The mucopolysaccharidoses (MPS disorders) are rare inherited diseases associated with multi-organ accumulation of glycosaminoglycans, leading to musculoskeletal, respiratory, cardiac, neurological, ophthalmological, otolaryngological, and gastrointestinal abnormalities. As a result of improvements in diagnosis, multi-disciplinary care, and therapies such as enzyme replacement therapy and hematopoietic stem cell transplantation, an increasing number of patients with MPS are reaching adulthood and are involved in family planning. Data on fertility and pregnancy outcome in MPS is sparse and comprises primarily isolated case reports. To address this evidence gap, we present a case series on fertility and pregnancy in eight mothers and five fathers with MPS. This case series demonstrates that women with MPS have high-risk pregnancies and deliveries secondary to their underlying disease. However, with appropriate pre-conceptual multi-disciplinary evaluation, optimization and discussion regarding potential risks, combined with regular multi-disciplinary maternal and fetal surveillance in a tertiary center, the outcome of most pregnancies in this case series seems to be favorable with all babies developing normally. Partners of fathers with MPS had uncomplicated pregnancies and deliveries. All children were healthy, with normal growth and development.

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