Sanfilippo Syndrome (Mucopolysaccharidosis Type III) Workup

Updated: Apr 19, 2023
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD  more...
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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 be performed by measuring for the specific enzymatic activity in cultured amniocytes or chorionic villi cells. [12]


Imaging Studies

Imaging studies include the following:

  • Neuroimaging to diagnosis hydrocephalus and to look for changes in brain structure 

    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


Other Tests

Other tests include the following:

  • 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