Genetics of Mucopolysaccharidosis Type II Follow-up

  • Author: Nancy E Braverman, MS, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Aug 5, 2011
 

Further Outpatient Care

  • A Hunter Outcome Survey was established by Shire to better understand the variability and progression of Hunter syndrome (mucopolysaccharidosis type II [MPS II]) and to monitor long-term treatment effects of Elaprase.
  • The authors encourage patient participation to gather additional data regarding response to enzyme replacement therapy (ERT). Both patients receiving treatment and those who are not can participate. As of May 2007, 263 patients from 16 countries were enrolled; 24% were being treated with ERT.[9]
  • Annual follow-up includes the following:
    • Echocardiography and ECG
    • Pulmonary function tests
    • Liver and spleen volume (MRI)
    • Skeletal survey
    • 6-minute walk test (every 6 mo)
    • Quality of life and pain assessment
    • Urinary glycosaminoglycan (GAG) level and iduronate sulfatase (IDS) antibody measurement
    • Audiography
    • Baseline sleep study, repeated as needed
    • CBC count, comprehensive metabolic panel, and routine urinalysis
Next

Complications

Various complications may arise in the severe form of MPS II, including cardiac valvular disease and neurological complications[35] .

  • Thickening of the tracheal walls may lead to obstructive airway disease.
  • As hepatosplenomegaly progresses, the abdominal wall becomes markedly distended, and hernias become more prominent.
  • All of the major joints, including the hips, knees, wrists, elbows, shoulders, and finger joints, become involved. This results in a decreased ability to pick up small objects, and, over time, walking becomes more difficult. The wrist is prone to carpal tunnel syndrome, which can further decrease hand function. One study evaluated the prevalence, clinical manifestation, and nerve conduction profiles in 45 male patients with CTS and Hunter syndrome. A significant difference was noted in age between hands with normal, mild, moderate, and severe grades of CTS, while the compound muscle action potential and sensory nerve action potential amplitudes of the median nerves decreased with age. The results suggest that mucopolysaccharidosis type II (Hunter syndrome) may contribute to CTS in children.[36]
  • Boney involvement occurs in MPS II, which may lead to short stature.
  • The Hunter Outcome Survey noted that 33% of patients develop hypertension, and neurological involvement is reported in 84% of patients (mostly behavioral and cognitive abnormalities).[9]
  • Another study evaluated the prevalence of cardiovascular manifestations in patients with Hunter syndrome. Using data from echocardiographic and electrocardiographic results from 102 patients who were enzyme replacement therapy – naïve in the Hunter Outcome Survey, the study found that while valve disease was the most common finding, left ventricular hypertrophy, elevated blood pressure, abnormal heart frequency, arrhythmia, and congestive heart failure were also noted.[37]
  • Using data from neurobehavioral standardized assessments of patients with mucopolysaccharidosis type II evaluated at the Program for Neurodevelopmental Function in Rare Disorders, one study sought to identify early clinical markers of neurologic involvement in mucopolysaccharidosis type II. The study results noted that subsequent cognitive dysfunction was strongly associated with sleep disturbance, increased activity, behavior difficulties, seizurelike behavior, perseverative chewing behavior, and an inability to achieve bowel and bladder training; a new severity score was also developed, with a score greater than or equal to 3 indicating a high likelihood of developing CNS disease.[38]
Previous
Next

Prognosis

  • The life expectancy for patients with the severe form (MPS IIA) is only about 10-15 years; however, those with the milder form (MPS-IIB) may live well into the seventh or eighth decades of life with supportive management.
  • After hematopoietic stem cell transplant, the characteristic cutaneous papules tend to regress, and most are gone by 3 months after the transplant.
Previous
Next

Patient Education

Support groups can be a good source of information for families, some of which include the following:

Other sources of information include the following:

Previous
 
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)

Cydney L Fenton, MD  Director, Center for Diabetes and Endocrinology, Akron Children's Hospital

Cydney L Fenton, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, Endocrine Society, and Pediatric Endocrine Society

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.

Specialty Editor Board

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: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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

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 and Genetics, Director RSA, 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.

Acknowledgments

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors William Rogers, MD, and Vinayak Kottoor, MD, to the original writing and development of this article.

References

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

  2. Timms KM, Lu F, Shen Y, et al. 130 kb of DNA sequence reveals two new genes and a regional duplication distal to the human iduronate-2-sulfate sulfatase locus. Genome Res. Aug 1995;5(1):71-8. [Medline].

  3. Timms KM, Bondeson ML, Ansari-Lari MA, et al. Molecular and phenotypic variation in patients with severe Hunter syndrome. Hum Mol Genet. Mar 1997;6(3):479-86. [Medline].

  4. Garcia AR, Pan J, Lamsa JC, Muenzer J. The characterization of a murine model of mucopolysaccharidosis II (Hunter syndrome). J Inherit Metab Dis. Sep 16 2007;[Medline].

  5. Matern D. Newborn screening for lysosomal storage disorders. Acta Paediatr Suppl. Apr 2008;97(457):33-7. [Medline].

  6. Lowry RB, Applegarth DA, Toone JR, MacDonald E, Thunem NY. An update on the frequency of mucopolysaccharide syndromes in British Columbia. Hum Genet. Aug 1990;85(3):389-90. [Medline].

  7. Schaap T, Bach G. Incidence of mucopolysaccharidoses in Israel: is Hunter disease a "Jewish disease"?. Hum Genet. 1980;56(2):221-3. [Medline].

  8. Young ID, Harper PS. Incidence of Hunter's syndrome. Hum Genet. 1982;60(4):391-2. [Medline].

  9. Wraith JE, Beck M, Giugliani R, Clarke J, Martin R, Muenzer J. Initial report from the Hunter Outcome Survey. Genet Med. Jul 2008;10(7):508-16. [Medline].

  10. Young ID, Harper PS. The natural history of the severe form of Hunter's syndrome: a study based on 52 cases. Dev Med Child Neurol. Aug 1983;25(4):481-9. [Medline].

  11. Clarke JT, Wilson PJ, Morris CP, et al. Characterization of a deletion at Xq27-q28 associated with unbalanced inactivation of the nonmutant X chromosome. Am J Hum Genet. Aug 1992;51(2):316-22. [Medline].

  12. Young ID, Harper PS, Newcombe RG, Archer IM. A clinical and genetic study of Hunter's syndrome. 2. Differences between the mild and severe forms. J Med Genet. Dec 1982;19(6):408-11. [Medline].

  13. Young ID, Harper PS. Mild form of Hunter's syndrome: clinical delineation based on 31 cases. Arch Dis Child. Nov 1982;57(11):828-36. [Medline].

  14. Spranger J, Cantz M, Gehler J, Liebaers I, Theiss W. Mucopolysaccharidosis II (Hunter disease) with corneal opacities. Report on two patients at the extremes of a wide clinical spectrum. Eur J Pediatr. Aug 17 1978;129(1):11-6. [Medline].

  15. Caruso RC, Kaiser-Kupfer MI, Muenzer J, Ludwig IH, Zasloff MA, Mercer PA. Electroretinographic findings in the mucopolysaccharidoses. Ophthalmology. Dec 1986;93(12):1612-6. [Medline].

  16. Beck M. Papilloedema in association with Hunter's syndrome. Br J Ophthalmol. Mar 1983;67(3):174-7. [Medline].

  17. Beck M, Cole G. Disc oedema in association with Hunter's syndrome: ocular histopathological findings. Br J Ophthalmol. Aug 1984;68(8):590-4. [Medline].

  18. Hobolth N, Pedersen C. Six cases of a mild form of Hunter syndrome in five generations. Three affected males with progeny. Clin Genet. 1978;20:121.

  19. Rozdzynska A, Tylki-Szymanska A, Jurecka A, Cieslik J. Growth pattern and growth prediction of body height in children with mucopolysaccharidosis type II. Acta Paediatr. Mar 2011;100(3):456-60. [Medline].

  20. Schulze-Frenking G, Jones SA, Roberts J, Beck M, Wraith JE. Effects of enzyme replacement therapy on growth in patients with mucopolysaccharidosis type II. J Inherit Metab Dis. Feb 2011;34(1):203-8. [Medline]. [Full Text].

  21. Isogai K, Sukegawa K, Tomatsu S, et al. Mutation analysis in the iduronate-2-sulphatase gene in 43 Japanese patients with mucopolysaccharidosis type II (Hunter disease). J Inherit Metab Dis. Feb 1998;21(1):60-70. [Medline].

  22. Crotty PL, Braun SE, Anderson RA, Whitley CB. Mutation R468W of the iduronate-2-sulfatase gene in mild Hunter syndrome (mucopolysaccharidosis type II) confirmed by in vitro mutagenesis and expression. Hum Mol Genet. Dec 1992;1(9):755-7. [Medline].

  23. Birot AM, Delobel B, Gronnier P, Bonnet V, Maire I, Bozon D. A 5-megabase familial deletion removes the IDS and FMR-1 genes in a male Hunter patient. Hum Mutat. 1996;7(3):266-8. [Medline].

  24. Hopwood JJ, Bunge S, Morris CP, et al. Molecular basis of mucopolysaccharidosis type II: mutations in the iduronate-2-sulphatase gene. Hum Mutat. 1993;2(6):435-42. [Medline].

  25. Rathmann M, Bunge S, Beck M, Kresse H, Tylki-Szymanska A, Gal A. Mucopolysaccharidosis type II (Hunter syndrome): mutation "hot spots" in the iduronate-2-sulfatase gene. Am J Hum Genet. Dec 1996;59(6):1202-9. [Medline].

  26. Clarke JT, Willard HF, Teshima I, Chang PL, Skomorowski MA. Hunter disease (mucopolysaccharidosis type II) in a karyotypically normal girl. Clin Genet. May 1990;37(5):355-62. [Medline].

  27. Kamin W. Diagnosis and management of respiratory involvement in Hunter syndrome. Acta Paediatr Suppl. Apr 2008;97(457):57-60. [Medline].

  28. Meikle PJ, Grasby DJ, Dean CJ, et al. Newborn screening for lysosomal storage disorders. Mol Genet Metab. Aug 2006;88(4):307-14. [Medline].

  29. Vellodi A, Young E, Cooper A, Lidchi V, Winchester B, Wraith JE. Long-term follow-up following bone marrow transplantation for Hunter disease. J Inherit Metab Dis. Jun 1999;22(5):638-48. [Medline].

  30. Mullen CA, Thompson JN, Richard LA, Chan KW. Unrelated umbilical cord blood transplantation in infancy for mucopolysaccharidosis type IIB (Hunter syndrome) complicated by autoimmune hemolytic anemia. Bone Marrow Transplant. May 2000;25(10):1093-7. [Medline].

  31. Martin R, Beck M, Eng C, et al. Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome). Pediatrics. Feb 2008;121(2):e377-86. [Medline].

  32. Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz TJ, Kimura A. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab. Mar 2007;90(3):329-37. [Medline].

  33. Muenzer J, Wraith JE, Beck M, et al. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. Aug 2006;8(8):465-73. [Medline].

  34. [Guideline] Wraith JE, Scarpa M, Beck M, et al. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. Mar 2008;167(3):267-77. [Medline].

  35. Al Sawaf S, Mayatepek E, Hoffmann B. Neurological findings in Hunter disease: pathology and possible therapeutic effects reviewed. J Inherit Metab Dis. Aug 2008;31(4):473-80. [Medline].

  36. Kwon JY, Ko K, Sohn YB, et al. High prevalence of carpal tunnel syndrome in children with mucopolysaccharidosis type II (Hunter syndrome). Am J Med Genet A. Jun 2011;155(6):1329-35. [Medline].

  37. Kampmann C, Beck M, Morin I, Loehr JP. Prevalence and characterization of cardiac involvement in hunter syndrome. J Pediatr. Aug 2011;159(2):327-331.e2. [Medline].

  38. Holt J, Poe MD, Escolar ML. Early Clinical Markers of Central Nervous System Involvement in Mucopolysaccharidosis Type II. J Pediatr. Aug 2011;159(2):320-326.e2. [Medline].

  39. Neufeld EF, Muenzer J. The Mucopolysaccharidoses. In: The Metabolic Bases of Inherited Disease. 8th ed. McGraw-Hill; 2000:3421-52.

 
Previous
Next
 
Clouding of the cornea.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.