The mucopolysaccharidoses are a group of inherited metabolic diseases caused by deficiencies in enzymes involved in the sequential degradation of glycosaminoglycans (GAGs) leading to substrate accumulation in various tissues and organs. GAG accumulation can cause growth retardation and progressive damage to respiratory, cardiovascular, musculoskeletal, nervous, gastrointestinal, auditory, and visual systems. In the past, few people with severe phenotypic mucopolysaccharidosis (MPS) reached adulthood. However, better methods for diagnosis, multi-disciplinary care, and new therapies have extended lifespan, leading to an increasing number of patients surviving beyond childhood. The growing number of adult MPS patients poses significant challenges for clinicians who may not be familiar with the clinical manifestations of MPS. In addition, as new interventions have changed the natural history of these disorders, it is difficult to anticipate both the impact on life expectancy and other complications that may occur as these patients age. Because the MPS disorders are multi-organ diseases, their management requires a coordinated multi-disciplinary approach. Here we discuss the unique pattern of medical issues and multi-organ involvement in adult patients with MPS and identify the challenges that are associated with management of MPS. This review is based on information from an expert investigator meeting with MPS specialists held October 2–4, 2014 in Dublin, Ireland, as well as on current literature searches focusing on MPS and adults.
Bibliographical noteFunding Information:
Dr. Mitchell has participated in BioMarin sponsored clinical trials. He has received travel support and consulting fees from BioMarin. Dr. Berger reports grants and personal fees for consultancy from BioMarin and Genzyme, during the conduct of the study; personal fees for consultancy from Teva, and Vertex outside the submitted work. Dr. Borgo reports personal fees from BioMarin, outside the submitted work. Dr. Braunlin reports personal fees for travel and lodging to participate in the expert meeting about MPS in adults from BioMarin Pharmaceutical Inc. associated with the submitted work; grants and non-financial support from BioMarin Pharmaceutical Inc. and consulting fees to her department from Ultragenyx, outside the submitted work. Dr. Burton reports personal fees and clinical trial support from BioMarin; grants, personal fees, and clinical trial support from Shire; personal fees and clinical trial support from Genzyme; personal fees from ReGenX Bio; and clinical trial support from Alexion, Ultragenyx, and Cytonet, outside the submitted work. Dr. Ghotme has nothing to disclose. Dr. Kircher reports personal fees for a lecture held at the Expert meeting about Adulthood and MPS and travel costs from BioMarin Pharmaceutical Inc., associated with the submitted work. Dr. Molter reports personal fees from BioMarin and grants and personal fees from Shire, outside the submitted work. Dr. Orchard reports grants and personal fees from Genzyme, grants from BioMarin, outside the submitted work. Dr. Palmer has nothing to disclose. Dr. Pastores reports an honorarium from BioMarin, during the conduct of the study and prior recipient of grants for the conduct of clinical trials from BioMarin and Genzyme (Sanofi) for enzyme replacement therapy in the mucopolysaccharidoses. Dr. Rapoport reports support from BioMarin for the Dublin meeting and for past consulting on some of the studies. Dr. Wang reports personal fees from BioMarin Pharmaceutical Inc., during the conduct of the study; personal fees and stock ownership from BioMarin Pharmaceutical Inc., outside the submitted work. Dr. White reports personal fees from BioMarin during the conduct of the study and outside the submitted work.
The authors are grateful to Ismar Healthcare NV for their assistance in writing of the manuscript, which was funded by BioMarin Pharmaceutical Inc. The current review is based on presentations and discussions from an expert meeting on MPS and adulthood that was held October 2–4, 2014 in Dublin, Ireland. This meeting was coordinated and funded by BioMarin Pharmaceutical Inc. The authors would like to thank all specialists who participated in this meeting.
- Disease management
- Enzyme replacement therapy
- Lysosomal storage diseases