Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Genetics of Mucopolysaccharidosis Type VII Clinical Presentation

  • Author: Maryam Banikazemi, MD; Chief Editor: Maria Descartes, MD  more...
 
Updated: Nov 10, 2015
 

History

Similar to most other mucopolysaccharidoses (MPSs), severity of symptoms in patients with MPS VII widely varies. Mucopolysaccharidosis type VII (MPS VII) is a progressive, debilitating, and often life-threatening disease that affects multiple organ-system.

In most severe cases, the condition presents as hydrops fetalis. Neonatal jaundice may be present at birth. Dysostosis multiplex is also associated with the severe form of Sly syndrome.

Coarse facial features with macrocephaly, hepatomegaly, hepatosplenomegaly, inguinal and umbilical hernias, and repeated upper respiratory infections may be observed.

Severe growth retardation may be prominent during the first 2 years of life in patients with severe disease.

In the milder forms of Sly syndrome, patients aged 4 years or older demonstrate symptoms.

Corneal opacities may develop at any time in patients older than 1 year.

Mental retardation is a common feature of Sly syndrome but is usually moderate and nonprogressive.

Next

Physical

Clinical presentation of MPS VIII includes the following:

  • Severe and early onset form (present at birth or during the first 4 y of life): This includes the prenatal form, as with nonimmune hydrops fetalis and severe neonatal forms presenting with neonatal cholestasis with hepatosplenomegaly.
  • Late onset (frequently in patients aged >4 y): Patients develop milder symptoms.

Major clinical manifestations include the following:

  • Dysmorphic features, such as coarse face, macrocephaly, frontal prominence, premature closure of sagittal lambdoid sutures, and short neck, may be observed.
  • Corneal clouding or opacity is also a feature, although it varies in age of onset. Iris colomba may be observed.
  • Visceral involvement and hepatosplenomegaly is a characteristic feature.
  • GI symptoms and ascites may develop.
  • Abnormal skeletal findings include short stature and dwarfism, dislocated hip, joint contractures, kyphoscoliosis, and wide rib cage/shield chest.
  • Connective tissue involvement includes inguinal and umbilical hernias and, rarely, vascular anomalies.
  • Growth and development is affected by presentation of postnatal short stature, hypotonia, and neurological disorders that ultimately lead to mental retardation. Mental retardation is often moderate, nonprogressive, and most pronounced in speech and language development.[4]
  • Lymphedema/edema, heart disease (eg valvar heart disease), and aortic regurgitation may develop.
  • Patients may develop hearing loss.
  • Patients may have signs of hirsutism.
  • Chronic inflammatory lung disease and recurrent respiratory infections are often a problem.
Previous
Next

Causes

See the list below:

  • Deficiency of the lysosomal enzyme b-glucuronidase
  • Accumulation of the undegraded mucopolysaccharides dermatan sulfate (DS), heparan sulfate (HS), and chondroitin sulfate (CS) in tissues and organs
  • Storage of excess mucopolysaccharides, contributing to numerous morphologic abnormalities
  • Genetic causes include the following:
    • The metabolic defect in patients with MPS VII has an autosomal recessive mode of inheritance (as is true of the other MPSs, except for MPS II or Hunter syndrome, which is transmitted as a sex-linked recessive trait).
    • Various mutations lead to a wide variety of phenotypes in patients with MPS VII.
    • The b-glucuronidase gene has been mapped to chromosome bands 7q21.11-q22.1.
Previous
 
 
Contributor Information and Disclosures
Author

Maryam Banikazemi, MD Assistant Professor of Clinical Pediatrics, New York Medical College

Maryam Banikazemi, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Coauthor(s)

Surendra Varma, MD, FAAP, FACE, DSc(Hon) Associate Dean for Graduate Medical Education and Resident Affairs, Ted Hartman Endowed Chair in Medical Education, University Distinguished Professor and Vice-Chair of Pediatrics, Professor of Physiology and Health Organization Management, Program Director Emeritus, Pediatric Residency Program, Texas Tech University Health Sciences Center School of Medicine

Surendra Varma, MD, FAAP, FACE, DSc(Hon) is a member of the following medical societies: Alpha Omega Alpha, Academic Pediatric Association, American Association of Clinical Endocrinologists, American Pediatric Society, Society for Pediatric Research, American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Sigma Xi, Texas Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

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 School of Medicine

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Karl S Roth, MD Retired 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 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, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Donald Nash, MD, to the development and writing of this article.

References
  1. Young RD, Liskova P, Pinali C, Palka BP, Palos M, Jirsova K, et al. Large proteoglycan complexes and disturbed collagen architecture in the corneal extracellular matrix of mucopolysaccharidosis type VII (Sly syndrome). Invest Ophthalmol Vis Sci. 2011 Aug. 52(9):6720-8. [Medline].

  2. de Ruijter J, de Ru MH, Wagemans T, Ijlst L, Lund AM, Orchard PJ, et al. Heparan sulfate and dermatan sulfate derived disaccharides are sensitive markers for newborn screening for mucopolysaccharidoses types I, II and III. Mol Genet Metab. 2012 Dec. 107(4):705-10. [Medline].

  3. Nelson J. Incidence of the mucopolysaccharidoses in Northern Ireland. Hum Genet. 1997 Dec. 101(3):355-8. [Medline].

  4. Wallace SP, Prutting CA, Gerber SE. Degeneration of speech, language, and hearing in a patient with mucopolysaccharidosis VII. Int J Pediatr Otorhinolaryngol. 1990 Jun. 19(2):97-107. [Medline].

  5. Smith LJ, Baldo G, Wu S, Liu Y, Whyte MP, Giugliani R, et al. Pathogenesis of lumbar spine disease in mucopolysaccharidosis VII. Mol Genet Metab. 2012 Sep. 107(1-2):153-60. [Medline]. [Full Text].

  6. Sly WS, Vogler C. Gene therapy for lysosomal storage disease: a no-brainer? Transplants of fibroblasts secreting high levels of beta-glucuronidase decrease lesions in the brains of mice with Sly syndrome, a lysosomal storage disease. Nat Med. 1997 Jul. 3(7):719-20. [Medline].

  7. Vellodi A, Young EP, Cooper A, et al. Bone marrow transplantation for mucopolysaccharidosis type I: experience of two British centres. Arch Dis Child. 1997 Feb. 76(2):92-9. [Medline].

  8. Fox JE, Volpe L, Bullaro J, Kakkis ED, Sly WS. First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient. Mol Genet Metab. 2015 Feb. 114 (2):203-8. [Medline].

  9. Emory AE, Rimoin DL, Connor JM, Pyeritz RE, eds. Emery and Rimoin's Principles and Practice of Medical Genetics. 3rd ed. Pearson Professional; 1996. 2077-8.

  10. McKusick VA. Gene 253220. Mendelian Inheritance in Man: A Catalog of Human Genes and Genetic Disorders. Vol 3. Johns Hopkins University Press; 1998.

  11. Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA. 1999 Jan 20. 281(3):249-54. [Medline].

  12. Nampoothiri S, Kappanayil M, Hiran KR, Sunitha V. Sly Disease Mucopolysaccharidosis Type VII. Indian Pediatr. 2008 Oct. 45(10):859-61. [Medline].

  13. Neufeld E, Muenzer J. The Mucopolysaccharidoses. Scriver C, Beaudet A, Sly W, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw Hill; 2001. 3421-52.

  14. Peters C, Shapiro EG, Anderson J, et al. Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. The Storage Disease Collaborative Study Group. Blood. 1998 Apr 1. 91(7):2601-8. [Medline].

  15. Wasant P, Wattanaweeradej S, Raksadawan N, Kolodny EH. Lysosomal storage disorders in Thailand: the Siriraj experience. Southeast Asian J Trop Med Public Health. 1995. 26 Suppl 1:54-8. [Medline].

  16. Whitley CB, Belani KG, Chang PN, Summers CG, Blazar BR, Tsai MY. Long-term outcome of Hurler syndrome following bone marrow transplantation. Am J Med Genet. 1993 Apr 15. 46(2):209-18. [Medline].

Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.