Persistent bone and joint disease despite current treatments for mucopolysaccharidosis types I, II, and VI: Data from a 10‐year prospective study

Abstract

The mucopolysaccharidosis (MPS) disorders have many potential new therapies on the horizon. Thus, historic control data on disease progression and variability are urgently needed. We conducted a 10‐year prospective observational study of 55 children with MPS IH (N = 23), MPS IA (N = 10), non‐neuronopathic MPS II (N = 13), and MPS VI (N = 9) to systematically evaluate bone and joint disease. Annual measurements included height, weight, and goniometry. Mixed effects modeling was used to evaluate changes over time. All participants had been treated with hematopoietic cell transplantation and/or enzyme replacement therapy. Height z‐score decreased over time in MPS IH, MPS II, and MPS VI, but not MPS IA. Adult heights were 136 ± 10 cm in MPS IH, 161 ± 11 cm in MPS IA, 161 ± 14 cm in MPS II, and 128 ± 15 cm in MPS VI. Adult average BMI percentiles were high: 75 ± 30%ile in MPS IH, 71 ± 37%ile in MPS IA, 71 ± 25%ile in MPS II, and 60 ± 42%ile in MPS VI. Every participant had joint contractures of the shoulders, elbows, hips, and/or knees. Joint contractures remained stable over time. In conclusion, despite current treatments for MPS I, II, and VI, short stature and joint contractures persist. The elevation in average BMI may be related, in part, to physical inactivity due to the ongoing bone and joint disease. Data from this longitudinal historical control study may be used to expedite testing of experimental bone and joint directed therapies and to highlight the need for weight management as part of routine clinical care for patients with MPS.

Evaluation of tendon and ligament microstructure and mechanical properties in a canine model of mucopolysaccharidosis I

“…While systemic treatments such as enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) have been shown to increase patient longevity, the response of joint disease, particularly in the lower extremities, is mixed, and surgical intervention is often indicated. [10][11][12][13] Furthermore, these therapies typically only prevent disease progression and do not reverse existing manifestations. 14,15 There is therefore a strong clinical need for improved treatment approaches that specifically target joint tissues; however, their development is hampered by poor understanding of underlying disease pathophysiology, including how pathological changes to component tissues contribute to overall joint dysfunction.…”

“…While not a direct source of patient mortality, joint manifestations therefore come at an immense personal cost to the quality of life of both patients and their carers. While systemic treatments such as enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) have been shown to increase patient longevity, the response of joint disease, particularly in the lower extremities, is mixed, and surgical intervention is often indicated 10–13 . Furthermore, these therapies typically only prevent disease progression and do not reverse existing manifestations 14,15 .…”