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Mucopolysaccharidosis Treatment & Management

  • Author: Tarek Bittar, MD; Chief Editor: Jeffrey D Thomson, MD  more...
 
Updated: Feb 02, 2016
 

Medical Care

Specific treatment or cure is limited for mucopolysaccharidosis (MPS). Management has been limited to supportive care and experimental treatment modalities. Routine assessment of multiple organ involvement is necessary to maintain the highest quality of life in these patients. Below are some of the medical and surgical treatment modalities that have been attempted for care of the patient with MPS.[5, 15, 16, 14, 8, 17]

Laronidase is a polymorphic variant of the human enzyme alpha-L-iduronidase produced by recombinant DNA technology. It is indicated to treat MPS type I (Hurler and Hurler-Scheie forms). It increases catabolism of glycosaminoglycans (GAGs), which accumulate with MPS I. Laronidase therapy has shown to improve walking capacity and pulmonary function.

Idursulfase is a purified form of human iduronate-2-sulfatase, a lysosomal enzyme. It hydrolyzes 2-sulfate esters of terminal iduronate sulfate residues from the GAGs dermatan sulfate and heparan sulfate in the lysosomes of various cell types. It is used to replace insufficient levels of the lysosomal enzyme iduronate-2-sulfatase in MPS II.[18, 16, 14, 8]

Elosulfase alfa was approved by the US Food and Drug Administration (FDA) in February 2014 for patients with Morquio A syndrome (mucopolysaccharidosis type IVA [MPS IVA]).[19, 20]

Severe handicapping hearing loss is present in about 70% of patients with MPS. Routine audiologic assessment and management is extremely important in order to maintain the highest quality of life.

Range-of-motion (ROM) exercises at home are indicated to limit the progressive loss of motion that is commonly seen in these patients. Night splinting and occupational aids have also been helpful.

Bone marrow transplantation (BMT) has been successful in the treatment of MPS conditions, especially Hurler syndrome. Children treated with BMT generally have an increased lifespan compared to untreated children. Untreated children commonly died of cardiorespiratory compromise in the first decade of life. However, the musculoskeletal condition (dysostosis multiplex) did not improve with BMT. Skeletal radiographs of children treated with BMT and those who are not treated typically look similar.[17]

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Surgical Care

Patients with mucopolysaccharidosis often require multiple common and uncommon surgeries and have a high postoperative mortality because of underlying respiratory and cardiac diseases.[21] Surgical care for specific conditions includes the following.

Hydrocephalus

Ventriculoperitoneal shunting is the surgical treatment of choice in the child with hydrocephalus. Some clinical improvement has been noted in these patients after shunting. However, neurologic dysfunction has not been significantly affected. Thus, early recognition of hydrocephalus and early shunting before the onset of severe neurologic involvement may play a role in the management of these patients.

Corneal clouding

Corneal transplantation has been performed for severe cases, but long-term results are lacking.

Cardiovascular disease

Valve replacement has been performed, but experience is only limited. Mitral and aortic valves are most affected.

Obstructive airway disease

Sleep apnea is common in MPS and is defined as cessation of airflow through the mouth or nose for a period longer than 10-15 seconds. Tracheostomy has been attempted for management of severe apnea with good success. Patients with obstructive airway disease are at a significant risk for anesthesia. This is especially true for patients with atlantoaxial instability, such as those with Morquio syndrome.

Orthopedic conditions

Orthopedic surgical procedures include soft-tissue and bony procedures. The most common soft-tissue procedure done in these patients is carpal tunnel release.

Soft-tissue procedures about the hip, knee, and ankle for release of contractures have also been performed, though results have been poor. Progressive hip subluxation, genu valgum and ankle valgus are common. Hip containment procedures (eg, femoral and pelvic osteotomies) are sometimes necessary in these patients.[22, 23] Progressive valgus deformity at the knee can be addressed with "guided growth" techniques. Severe deformities may also necessitate corrective osteotomy, usually of the proximal tibia. Ankle valgus can be also be treated with guided growth techniques.

Kyphosis is progressive in many of these patients, especially at the thoracolumbar level and sometimes associated with thoracic scoliosis.[24] Posterior spinal fusion is proved to prevent further progression. In the cervical spine, odontoid hypoplasia can be seen leading to atlantoaxial instability. Fusion from C1 to C3 can be helpful.

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Consultations

Multispecialty care is mandatory for these patients and should include the following:

  • Pediatrician (internist)
  • Neurologist
  • Cardiologist
  • Ophthalmologist
  • Audiologist
  • Orthopedic surgeon
  • Physical and occupational therapist
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Contributor Information and Disclosures
Author

Tarek Bittar, MD Staff Physician, Department of Orthopedic Surgery, Martin Luther King Medical Center

Tarek Bittar, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons

Disclosure: Nothing to disclose.

Coauthor(s)

Eleby R Washington, III, MD, FACS Associate Professor, Department of Surgery, Division of Orthopedics, Charles R Drew University of Medicine and Science

Eleby R Washington, III, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, American Medical Association, International College of Surgeons, National Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

George H Thompson, MD Director of Pediatric Orthopedic Surgery, Rainbow Babies and Children’s Hospital, University Hospitals Case Medical Center, and MetroHealth Medical Center; Professor of Orthopedic Surgery and Pediatrics, Case Western Reserve University School of Medicine

George H Thompson, MD is a member of the following medical societies: American Orthopaedic Association, Scoliosis Research Society, Pediatric Orthopaedic Society of North America, American Academy of Orthopaedic Surgeons

Disclosure: Received none from OrthoPediatrics for consulting; Received salary from Journal of Pediatric Orthopaedics for management position; Received none from SpineForm for consulting; Received none from SICOT for board membership.

Chief Editor

Jeffrey D Thomson, MD Associate Professor, Department of Orthopedic Surgery, University of Connecticut School of Medicine; Director of Orthopedic Surgery, Department of Pediatric Orthopedic Surgery, Associate Director of Clinical Affairs for the Department of Surgical Subspecialties, Connecticut Children’s Medical Center; President, Connecticut Children's Specialty Group

Jeffrey D Thomson, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons

Disclosure: Nothing to disclose.

Additional Contributors

Charles T Mehlman, DO, MPH Professor of Pediatrics and Pediatric Orthopedic Surgery, Division of Pediatric Orthopedic Surgery, Director, Musculoskeletal Outcomes Research, Cincinnati Children's Hospital Medical Center

Charles T Mehlman, DO, MPH is a member of the following medical societies: American Academy of Pediatrics, American Fracture Association, Scoliosis Research Society, Pediatric Orthopaedic Society of North America, American Medical Association, American Orthopaedic Foot and Ankle Society, American Osteopathic Association, Arthroscopy Association of North America, North American Spine Society, Ohio State Medical Association

Disclosure: Nothing to disclose.

References
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  2. Jones KL. Storage disorders. In: Smith's Recognizable Patterns of Human Malformation. Philadelphia, Pa: WB Saunders Co; 1997:456-471.

  3. Muenzer J. Mucopolysaccharidoses. Adv Pediatr. 1986. 33:269-302. [Medline].

  4. Tandon V, Williamson JB, Cowie RA. Spinal problems in mucopolysaccharidosis I (Hurler syndrome). J Bone Joint Surg Br. 1996 Nov. 78(6):938-44. [Medline].

  5. Masterson EL, Murphy PG, O'Meara A, Moore DP, Dowling FE, Fogarty EE. Hip dysplasia in Hurler's syndrome: orthopaedic management after bone marrow transplantation. J Pediatr Orthop. 1996 Nov-Dec. 16(6):731-3. [Medline].

  6. Dupont C, Hachem CE, Harchaoui S, Ribault V, Amiour M, Guillot M. [Hurler syndrome: Early diagnosis and successful enzyme replacement therapy: A new therapeutic approach. Case report.]. Arch Pediatr. 2008 Jan. 15(1):45-49. [Medline].

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  8. Wraith JE, Scarpa M, Beck M, Bodamer OA, De Meirleir L, Guffon N. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008 Mar. 167(3):267-277. [Medline].

  9. Burton BK, Giugliani R. Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls. Eur J Pediatr. 2012 Apr. 171(4):631-9. [Medline]. [Full Text].

  10. Menkès CJ, Rondot P. Idiopathic osteonecrosis of femur in adult Morquio type B disease. J Rheumatol. 2007 Nov. 34(11):2314-6. [Medline].

  11. Tong CK, Chen JC, Cochrane DD. Spinal cord infarction remote from maximal compression in a patient with Morquio syndrome. J Neurosurg Pediatr. 2012 Jun. 9(6):608-12. [Medline].

  12. Thümler A, Miebach E, Lampe C, Pitz S, Kamin W, Kampmann C, et al. Clinical characteristics of adults with slowly progressing mucopolysaccharidosis VI: a case series. J Inherit Metab Dis. 2012 Nov. 35(6):1071-9. [Medline].

  13. Rosselli D, Rueda JD, Solano M. Ethical and economic considerations of rare diseases in ethnic minorities: the case of mucopolysaccharidosis VI in Colombia. J Med Ethics. 2012 May 1. [Medline].

  14. Tolar J, Grewal SS, Bjoraker KJ, Whitley CB, Shapiro EG, Charnas L. Combination of enzyme replacement and hematopoietic stem cell transplantation as therapy for Hurler syndrome. Bone Marrow Transplant. 2007 Nov 26. [Medline].

  15. Chan YL, Lin SP, Man TT. Clinical experience in anesthetic management for children with mucopolysaccharidoses: Report of ten cases. Acta Paediatr Taiwan. 2001 Sep-Oct. 42(5):306-8. [Medline].

  16. Tomatsu S, Montaño AM, Ohashi A, Oikawa H, Oguma T, Dung VC. Enzyme replacement therapy in a murine model of Morquio A syndrome. Hum Mol Genet. 2007 Dec 3. [Medline].

  17. Guffon N, Souillet G, Maire I, et al. Follow-up of nine patients with Hurler syndrome after bone marrow transplantation. J Pediatr. 1998 Jul. 133(1):119-25. [Medline].

  18. Clarke LA. Idursulfase for the treatment of mucopolysaccharidosis II. Expert Opin Pharmacother. 2008 Feb. 9(2):311-7. [Medline].

  19. FDA news release. FDA approves Vimizim to treat rare congenital enzyme disorder. February 14, 2014. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm386008.htm. Accessed: February 25, 2014.

  20. A Double-Blind Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome). NCT01275066. ClinicalTrials.gov. Available at http://clinicaltrials.gov/ct2/show/study/NCT01275066. Accessed: February 20, 2014.

  21. Arn P, Whitley C, Wraith JE, Webb HW, Underhill L, Rangachari L, et al. High rate of postoperative mortality in patients with mucopolysaccharidosis I: findings from the MPS I Registry. J Pediatr Surg. 2012 Mar. 47(3):477-84. [Medline].

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An 8-year-old boy with Morquio syndrome and severe kyphoscoliosis. Courtesy of Dennis P. Grogan, MD.
A 7-year-old girl with Morquio syndrome and typical severe genu valgum. Courtesy of Dennis P. Grogan, MD.
Morquio syndrome; widened bases of phalanges with osteopenia. Courtesy of Bruce M. Rothschild, MD.
Morquio syndrome; lateral radiograph of thoracolumbar vertebrae illustrates vertebral body beaking. Courtesy of Bruce M. Rothschild, MD.
Hurler syndrome; lateral radiograph of thoracolumbar vertebrae illustrates vertebral plana. Courtesy of Bruce M. Rothschild, MD.
Morquio syndrome; anteroposterior radiograph of pelvis illustrates avascular necrosis of femoral head. Courtesy of Bruce M. Rothschild, MD.
Hurler syndrome; widened metaphyses and diaphyses with truncated distal portions forming a peg characterize this radiograph. Courtesy of Bruce M. Rothschild, MD.
Hurler syndrome; widened metaphyses and diaphyses with truncated distal portions forming a peg characterize this radiograph. Courtesy of Bruce M. Rothschild, MD.
 
 
 
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