- Simon Jones, MD
Simon Jones, MD
- Honorary Senior Lecturer
- University of Manchester
- Consultant in Paediatric Inborn Errors of Metabolism
- Manchester Centre for Genomic Medicine
- Robert Wynn, MD, MRCP, FRCPath
Robert Wynn, MD, MRCP, FRCPath
- Consultant in Paediatric Haematology and Blood and Marrow Transplantation
- Royal Manchester Children's Hospital
- Section Editors
- Sihoun Hahn, MD, PhD
Sihoun Hahn, MD, PhD
- Section Editor — Genetics
- Professor of Pediatrics
- University of Washington School of Medicine, Seattle Children's Hospital
- Marc C Patterson, MD, FRACP
Marc C Patterson, MD, FRACP
- Section Editor — Pediatric Neurology
- Professor of Neurology, Pediatrics, and Medical Genetics
- Chair, Division of Child and Adolescent Neurology
- Mayo Clinic College of Medicine
The mucopolysaccharidoses (MPS) are lysosomal storage disorders caused by the deficiency of enzymes required for the stepwise breakdown of glycosaminoglycans (GAGs), also known as mucopolysaccharides. These conditions are differentiated by their clinical features and age of presentation (table 1). The MPS can affect many different systems, including the respiratory, cardiovascular, skeletal, and neurologic systems. Enzyme replacement therapy (ERT) is available for some MPS. Other therapies focus on treatment of symptoms.
Treatment of the MPS is reviewed here. The clinical features and diagnosis of these disorders as well as associated complications are discussed separately. (See "Mucopolysaccharidoses: Clinical features and diagnosis" and "Mucopolysaccharidoses: Complications".)
OVERVIEW OF MANAGEMENT
Most therapies for MPS are directed toward treatment of complications and are not specific for the underlying abnormality. Supportive or symptomatic management can improve the quality of life for patients and their families, but they cannot prevent the inevitable decline in function. However, specific therapies, such as enzyme replacement or hematopoietic cell transplantation, may alter the natural history of these disorders. The choice of therapy depends upon the type of MPS and the disease severity in the specific patient. Management of complications is discussed in detail separately. (See "Mucopolysaccharidoses: Complications".)
ENZYME REPLACEMENT THERAPY
Enzyme replacement therapy (ERT) is approved in the United States (US), European Union (EU), and several other countries for patients with MPS I, MPS II, MPS IVA, and MPS VI (table 1) . Indications vary across the MPS, but generally ERT is used in patients with moderate to severe disease. The exception is patients <2 years of age with severe MPS I (Hurler), for whom hematopoietic cell transplantation is preferred if there is a suitable donor (see 'Hematopoietic cell transplantation' below). Clinical trials are underway for ERT for MPS VII.
MPS I — In patients with MPS I (Hurler, Hurler-Scheie, and Scheie syndromes), treatment with recombinant human alpha-L-iduronidase (laronidase), the deficient enzyme, reduces lysosomal storage in the liver and improves some clinical manifestations while stabilizing others [2-6]. Better outcome is achieved if laronidase is initiated before serious complications occur [6,7]. The recommended dose is 0.58 mg/kg (rounded up to the nearest whole vial) given intravenously (IV) once a week.
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