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Genetics of Mucopolysaccharidosis Type III Workup

  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD  more...
 
Updated: Oct 05, 2015
 

Laboratory Studies

Biochemical differentiation of the different subtypes of mucopolysaccharidosis (MPS) type III is possible, and diagnosis is confirmed by specific enzymatic assay.

Enzymatic activity for all subtypes of Sanfilippo syndrome can be assayed in cultured skin fibroblasts and in peripheral blood leukocytes. If mucopolysaccharidosis type III is suspected, enzymatic cell analysis is the recommended test.

In all subtypes of mucopolysaccharidosis type III, urinary excretion of heparan sulfate is increased. To measure the concentration of glycosaminoglycans or glycosaminoglycans (GAGs) in the urine, a total quantitative test and a fractionation test should be performed using electrophoresis or chromatography. Ideally, a first-morning urine specimen should be analyzed because a concentrated urine specimen is needed to avoid a false-negative result due to dilutional effect. This sample recommendation is especially important for the diagnosis of mucopolysaccharidosis type III because of the low urinary GAG levels and smaller heparan fragments seen in this syndrome. Urinary GAG levels are higher in newborns and infants than in older children. Interpretation of results must include age-specific controls and fractionation to properly identify pathologic GAG levels (ie, heparan sulfate) from normal GAG levels present in the urine (ie, chondroitins).

Prenatal diagnosis can also be performed by measuring for the specific enzymatic activity in cultured amniocytes or chorionic villi cells.[12]

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Imaging Studies

See the list below:

  • Neuroimaging to diagnosis hydrocephalus and to look for changes in brain structure (See the image below)
    Noncommunicating obstructive hydrocephalus caused Noncommunicating obstructive hydrocephalus caused by obstruction of the foramina of Luschka and Magendie. This MRI sagittal image demonstrates dilatation of lateral ventricles with stretching of corpus callosum and dilatation of the fourth ventricle.
  • Echocardiography to assess for asymmetric septal hypertrophy, cardiomegaly, and valvular disease
  • Abdominal imaging, such as ultrasonography or CT scanning, to evaluate for organomegaly
  • Radiographic skeletal survey to identify cases of dysostosis multiplex
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Other Tests

See the list below:

  • Electroencephalography (EEG) to diagnose seizure activity
  • Audiologic evaluation to identify patients with hearing loss
  • Polysomnography for those patients who demonstrate clinical signs of airway obstruction due to anatomical changes, such as obstructive sleep apnea
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Contributor Information and Disclosures
Author

Germaine L Defendi, MD, MS, FAAP Associate Clinical Professor, Department of Pediatrics, Olive View-UCLA Medical Center

Germaine L Defendi, MD, MS, FAAP is a member of the following medical societies: American Academy of Pediatrics

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 Medscape Reference gratefully acknowledge the contributions of previous author Donald Nash to the original writing and development of this article.

References
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Noncommunicating obstructive hydrocephalus caused by obstruction of the foramina of Luschka and Magendie. This MRI sagittal image demonstrates dilatation of lateral ventricles with stretching of corpus callosum and dilatation of the fourth ventricle.
 
 
 
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