Genetics of Mucopolysaccharidosis Type III Workup

  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Mar 22, 2012
 

Laboratory Studies

  • Biochemical differentiation of the different forms within mucopolysaccharidosis type III (MPS III) is possible, and diagnosis is confirmed by specific enzymatic assay.
  • Enzymatic activity for all types of Sanfilippo syndrome may be assayed in cultured skin fibroblasts and in peripheral blood leukocytes. If mucopolysaccharidosis III is suspected, enzymatic cell analysis is the recommended test.
  • In all forms of mucopolysaccharidosis III, urinary excretion of heparan sulfate is increased.
    • To measure the concentration of GAGs in the urine, a total quantitative test and a fractionation test should be performed using electrophoresis or chromatography.
    • A concentrated urine specimen is best to avoid a false-negative result due to a dilute urine. Ideally, a first-morning urine specimen should be analyzed. This is especially important for the diagnosis of mucopolysaccharidosis 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.[11]
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Imaging Studies

  • 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 and valvular disease
  • Imaging of the abdomen, such as ultrasonography or CT scanning, to evaluate for organomegaly
  • Radiographic skeletal survey to identify cases of dysostosis multiplex (the spectrum of skeletal changes seen in patients with mucopolysaccharidosis disorders)
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Other Tests

  • Electroencephalography (EEG) to diagnose seizure activity
  • Audiologic evaluation to identify patients with hearing loss
  • Polysomnography for those patients who demonstrate clinical signs of 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  Associate Dean, Graduate Medical Education and Resident Affairs, Ted Hartman Endowed Chair in Medical Education, University Distinguished Professor and Vice-Chairman of Pediatrics, Professor of Physiology and Health Organization Management, Director, Pediatric Residency Program, Texas Tech University Health Sciences Center School of Medicine

Surendra Varma, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Medical Association, American Thyroid Association, Endocrine Society, Medical Group Management Association, New York Academy of Sciences, Sigma Xi, Society for Pediatric Radiology, Southern Society for Pediatric Research, and Texas Medical Association

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.

Additional Contributors

The authors and editors of eMedicine 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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