eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Mucopolysaccharidosis Type II: Treatment & Medication

Author: Nancy E Braverman, MS, MD, Associate Professor, Department of Human Genetics, McGill University
Coauthor(s): Vinayak Kottoor, MD, Resident, Department of Genetics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University Hospital; Mary Kay Conover-Walker, MSN, PNP, Pediatric Nurse Practioner, Institute of Genetic Medicine, Johns Hopkins Hospital; Cydney L Fenton, MD, FAAP, Consulting Staff, Department of Pediatric Endocrinology, Children's Hospital Medical Center of Akron
Contributor Information and Disclosures

Updated: Jul 14, 2009

Treatment

Medical Care

Although no curative treatment for lysosomal storage disorders is available, numerous treatment options are becoming available to improve the quality of life in these patients. The relevant enzyme (iduronate sulfatase [IDS] in the case of mucopolysaccharidosis type II [MPS II]) can be given in the form of enzyme replacement therapy (ERT) or by bone marrow transplantation (BMT). Factors that affect outcome include the type of MPS, the donor genotype (in the case of BMT), and the age and degree of clinical involvement at the start of therapy or transplantation.  

In order to identify individuals that might benefit from treatment before the onset of irreversible organ damage, newborn screening for these disorders is being developed.26  Gene therapy is a promising but inadequately developed modality of treatment. Difficulties with vector selection and efficiency of delivery persist; thus, this therapy is still in the early stages of development.

  • BMT
    • In 16 children with Hunter syndrome who have undergone BMT, marked deterioration in mental retardation continued in 15.27 All 15 children had intelligence quotients that fell below 50. Some of these children did have improvement in their somatic symptoms, with a decrease in the coarsening of their face and hair and an increase in the range of motion in their joints. The hearing deficits may not improve after BMT.
    • In addition to the study of BMT, the use of umbilical cord blood transplantation from an unrelated donor has been attempted at least once.28
  • ERT: See Medication.

Surgical Care

  • Many children with Hunter syndrome require surgical intervention for complications of their disorder. These include intervention for chronic hydrocephalus, nerve entrapment (carpal tunnel syndrome), abdominal wall hernias, tracheostomy, and joint contractures.
  • Individuals with Hunter syndrome should undergo anesthesia at a center with experienced personnel.
  • Problems can occur with airway management, postobstructive pulmonary edema, and reactive airway disease.

Consultations

  • Care for the patient with Hunter syndrome involves a multidisciplinary approach and includes pediatricians, neurologists, orthopedists, otolaryngologists, ophthalmologists, and occupational and physical therapists, as well as geneticists and counselors.
  • The recognition and diagnosis of MPS II was recently reviewed.29

Medication

Idursulfase, a purified form of human iduronate sulfatase (IDS) was approved by the US Food and Drug Administration (FDA) as an orphan drug in July 2006. It is distributed as Elaprase (Shire Human Genetics Therapies, Inc). FDA approval was based on the study of 96 patients in a double-blind, placebo-controlled study over one year.30,31 This study demonstrated improvement in a 6-minute walk test and reduction in liver and spleen volumes and urinary glycosaminoglycan (GAG) levels.

The extent to which enzyme replacement therapy (ERT) delays disease progression and whether or not it can prevent premature death is still unknown. Severely affected patients were not enrolled, and thus the benefit to them remains to be determined. ERT does not enter the CNS and has no impact on cognitive function. Thus, the role of ERT in the management of Hunter syndrome is under debate.32

Enzymes

ERT is a life-long therapy that may improve the quality of life for patients with mucopolysaccharidosis type II (MPS II).


Idursulfase (Elaprase)

Purified form of human iduronate-2-sulfatase, a lysosomal enzyme. Hydrolyzes 2-sulfate esters of terminal IDS residues from the GAGs dermatan sulfate and heparan sulfate in the lysosomes of various cell types. Indicated for MPS II (Hunter syndrome) because it replaces the deficiency of iduronate-2-sulfatase in this disease. The drug is continued throughout life, and, thus, both the time and financial commitment can be extensive. Administration should be done by a health care professional in an experienced infusion center.

Adult

0.5 mg/kg IV qwk; total volume typically infused over 1-3 h, although longer infusion time (up to 8 h) may be required because of infusion reactions; initiate at rate of 8 mL/h for first 14 min, if tolerated may increase by 8-mL/h increments q15min; not to exceed 100 mL/h;
If an infusion reaction occurs, infusion may be slowed, temporarily stopped, or discontinued for the visit, based on clinical judgment

Pediatric

<5 years: Not established
>5 years: Administer as in adults

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Anaphylactoid reactions have occurred (additional monitoring required, especially for individuals with respiratory compromise); appropriate medical support should be available during infusion, and premedication with antihistamines, corticosteroids, or both recommended prior to infusion; common adverse effects include infusion-related reactions (eg, pyrexia, headache, arthralgia, pruritus, malaise, visual disturbance, musculoskeletal pain, urticaria); about 50% of patients in clinical studies produced anti-idursulfase IgG antibodies during treatment, and these patients had an increase in infusion reactions; the presence of antibodies on the effectiveness is unknown

More on Mucopolysaccharidosis Type II

Overview: Mucopolysaccharidosis Type II
Differential Diagnoses & Workup: Mucopolysaccharidosis Type II
Treatment & Medication: Mucopolysaccharidosis Type II
Follow-up: Mucopolysaccharidosis Type II
Multimedia: Mucopolysaccharidosis Type II
References
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References

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Further Reading

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Keywords

mucopolysaccharidosis type II, Hunter syndrome, MPS II, type A MPS II, type B MPS II, iduronate sulfatase deficiency, lysosomal enzyme deficiency, dysostosis multiplex, lysosomal storage disorders, coarse facial features, corneal clouding, thickened skin, organomegaly, mental retardation, growth failure, skeletal dysplasia, upper airway obstruction, carpal tunnel syndrome, short stature, hyperactivity, progressive hearing loss, hepatomegaly, progressive retinal degeneration, recurrent ear infections, hydrocephalus

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Contributor Information and Disclosures

Author

Nancy E Braverman, MS, MD, Associate Professor, Department of Human Genetics, McGill University
Nancy E Braverman, MS, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Human Genetics, Society for Inherited Metabolic Disorders, and Society for the Study of Inborn Errors of Metabolism
Disclosure: Nothing to disclose.

Coauthor(s)

Vinayak Kottoor, MD, Resident, Department of Genetics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University Hospital
Disclosure: Nothing to disclose.

Mary Kay Conover-Walker, MSN, PNP, Pediatric Nurse Practioner, Institute of Genetic Medicine, Johns Hopkins Hospital
Mary Kay Conover-Walker, MSN, PNP is a member of the following medical societies: American Academy of Allergy Asthma and Immunology and Association of Clinical Research Professionals
Disclosure: Nothing to disclose.

Cydney L Fenton, MD, FAAP, Consulting Staff, Department of Pediatric Endocrinology, Children's Hospital Medical Center of Akron
Cydney L Fenton, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Clinical Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, and Southern Society for Pediatric Research
Disclosure: MDS Pharma Salary Employment

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Margaret M McGovern, MD, PhD, Professor and Chair of Pediatrics, Stony Brook University, New York
Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics
Disclosure: Genzyme Grant/research funds PI

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
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