Genetics of Mucopolysaccharidosis Type II Workup

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

Laboratory Studies

  • Urine spot tests are readily available to screen for mucopolysaccharidoses (MPSs). These tests are associated with false-positive and false-negative results; testing more than one urine sample is recommended.
  • Semiquantification of urinary glycosaminoglycan (GAG) can be obtained by spectrophotometric assays with dimethylmethylene blue.
  • Heparan sulfate, keratan sulfate (KS), and dermatan sulfate can be distinguished by electrophoretic techniques to narrow the differential among the MPSs.
  • Clinical suspicion should take precedence over screening test results because the results vary.
  • A new enzyme-linked immunoassay (ELISA) technique has recently been shown to accurately quantify GAGs in urine and blood.
  • Lysosomal enzymes are present in all cells except mature erythrocytes.
  • The diagnosis is confirmed by direct enzymatic assay in leukocytes or fibroblasts.
  • The enzyme deficient in Hunter syndrome is iduronate-2-sulfatase. In males without a family history, normal activity of another sulfatase is required to rule out multiple sulfatase deficiency.
  • University hospitals with expertise in metabolic genetics perform these assays on heparinized blood or fibroblasts cultured from a small (2 mm) skin biopsy.
  • For prenatal diagnosis, enzyme activity can be measured in amniocytes or chorionic villi. Determination of the carrier state by enzyme analysis is not always possible because the range of enzyme activity in noncarriers and carriers overlaps. Carriers can be diagnosed by molecular analysis of the IDS gene. Usually the mutation is first identified in the affected proband.
  • GeneTests lists several institutions that offer enzymatic and mutation analysis for Hunter syndrome. Obtaining specific instructions from the laboratory performing these assays prior to collecting samples from patients is beneficial.
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Imaging Studies

  • A full skeletal survey should be obtained in a patient with suspected MPS. The following views are recommended:
    • Anteroposterior (AP) and lateral views of the skull with visualization of the sella
    • Flexion and extension radiographs of the cervical spine
    • AP and lateral views of the odontoid
    • AP and lateral views of the chest
    • Standing AP and lateral views of entire spine
    • Standing pelvis view with visualization of the femoral heads articulating with the acetabulum
    • Preferably, standing AP views of the lower extremities, including the entire femur, articulation with tibia (knees for genu valgus), and ankles
    • AP views of at least one foot, one hand, forearm, elbow in extension, humerus, and shoulder
  • CT scanning or MRI of the brain stem and cervical spine should be performed to evaluate odontoid hypoplasia and cord compression. The authors recommend additional cerebrospinal fluid (CSF) flow studies in flexion and extension in older patients as indicated.
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Other Tests

  • Ophthalmologic examination: An ophthalmology examination with slit lamp should be performed at the time of initial evaluation to look for corneal and retinal disease.
  • Cardiac echocardiography and ECG
  • Airway evaluation: This is performed to assess for upper airway obstruction, sleep apnea, and pulmonary functions.[27]
  • Audiology evaluation
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Histologic Findings

  • Histologic examination of either peripheral granulocytes or bone marrow cells may reveal Alder-Reilly granulations.
  • When stained with toluidine blue, peripheral lymphocytes exhibit metachromatic granules within vacuoles.
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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)

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.

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