Hunter Syndrome (Mucopolysaccharidosis Type II) Workup

Updated: Apr 18, 2018
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD  more...
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Workup

Laboratory Studies

Clinical suspicion should take precedence over screening test results because laboratory results can vary.

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 GAGs 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 diagnostic differential among the MPSs.A new enzyme-linked immunoassay (ELISA) technique has recently been shown to accurately quantify GAGs in urine (eg, dermatan and heparan sulfate excretion) and in blood.

Lysosomal enzymes are present in all cells except mature erythrocytes. The enzyme deficient in Hunter syndrome is iduronate-2-sulfatase. Iduronate sulfatase deficiency is determined by the direct enzymatic assay of leucocytes and fibroblasts. Academic medical facilities 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 enzyme mutation is first identified in the affected proband.

GeneTests lists several institutions that offer enzymatic and mutation analysis for Hunter syndrome. Prior to obtaining laboratory samples from patients, it is important to obtain collection and transport instructions from the laboratory performing these assays.

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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 for odontoid hypoplasia and cord compression. Additional cerebrospinal fluid (CSF) flow studies in both flexion and extension positions may be indicated in older patients. 

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Other Tests

Other tests include the following:

  • Ophthalmologic examination with slit lamp: evaluation to assess visual acuity and corneal and retinal disease.
  • Audiology evaluation
  • Cardiac echocardiography and ECG
  • Airway evaluation: Assess for upper airway obstruction and sleep apnea and determine pulmonary function. [31]
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Histologic Findings

Histologic examination of either peripheral granulocytes or bone marrow cells may show Alder-Reilly granulations. Peripheral lymphocytes exhibit metachromatic granules within vacuoles when stained with toluidine blue.

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