Mucopolysaccharidosis Workup

Updated: Mar 06, 2018
  • Author: Tarek Bittar, MD; Chief Editor: Jeffrey D Thomson, MD  more...
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Workup

Laboratory Studies

Antenatal screening

Chorionic villus sampling is performed around week 9 of pregnancy and has become increasingly popular for the diagnosis of mucopolysaccharidosis (MPS).

Antenatal diagnosis of MPS conditions (with the exception of Hunter syndrome) can be made by measuring the enzyme activity in cultured amniotic cells. Amniocentesis commonly is performed in the 15th to 16th week of gestation. Heterozygote identification is important in Hunter syndrome and can be done with hair-root analysis and single-cell cloning of fibroblasts. However, these procedures are not widely available.

Postnatal diagnosis

Urine analysis is useful because excessive urinary excretion of glycosaminoglycans (GAGs) is the basis for screening tests for MPS. Serum assays are useful because lysosomal enzymes can be assayed in serum, leukocytes, or cultured cells. These assays for different lysosomal enzymes are taken for all patients thought to have MPS.

Assays for MPS IH (Hurler syndrome) are as follows [7, 15] :

  • Enzyme deficiency - Alpha-L-Iduronidase
  • Urinary glycosaminoglycan (GAG) - Dermatan sulfate, heparan sulfate

Assays for MPS I-H/S (Hurler-Scheie syndrome) are as follows:

  • Enzyme deficiency - Alpha-L-Iduronidase
  • Urinary GAG - Dermatan sulfate, heparan sulfate

Assays for MPS IS (Scheie syndrome) are as follows:

  • Enzyme deficiency - Alpha-L-Iduronidase
  • Urinary GAG - Dermatan sulfate, heparan sulfate

Assays for MPS II-A (Hunter syndrome, severe) [8]  are as follows:

  • Enzyme deficiency - Iduronate sulfatase
  • Urinary GAG - Dermatan sulfate, heparan sulfate

Assays for MPS II-B (Hunter syndrome, mild) [8]  are as follows:

  • Enzyme deficiency - Iduronate sulfatase
  • Urinary GAG - Dermatan sulfate, heparan sulfate

Assays for MPS III-A (Sanfilippo syndrome A) are as follows:

  • Enzyme deficiency - Heparan N -sulfatase
  • Urinary GAG - Heparan sulfate

Assays for MPS III-B (Sanfilippo syndrome B) are as follows:

  • Enzyme deficiency - N-acetylglucosaminidase
  • Urinary GAG - Heparan sulfate

Assays for MPS III-C (Sanfilippo syndrome C) are as follows:

  • Enzyme deficiency - Acetyl-coenzyme A: Alpha-glucosamine- N-acetyltransferase
  • Urinary GAG - Heparan sulfate

Assays for MPS III-D (Sanfilippo syndrome D) are as follows:

  • Enzyme deficiency - N-acetyl alpha-glucosamine-6-sulfatase
  • Urinary GAG - Heparan sulfate

Assays for MPS IV-A (Morquio syndrome A) are as follows:

  • Enzyme deficiency - N-acetylgalactosamine-6-sulfatase
  • Urinary GAG - Keratan sulfate

Assays for MPS IV-B (Morquio syndrome B) are as follows:

  • Enzyme deficiency - B-galactosidase
  • Urinary GAG - Keratan sulfate

Assays for MPS VI (Maroteaux-Lamy syndrome) are as follows:

  • Enzyme deficiency - N-acetylgalactosamine-4-sulfatase
  • Urinary GAG - Dermatan sulfate

Assays for MPS VII (Sly syndrome) are as follows:

  • Enzyme deficiency - B-glucuronidase
  • Urinary GAG - Dermatan sulfate, heparan sulfate
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Imaging Studies

Dysostosis multiplex refers to a constellation of skeletal abnormalities in MPS conditions diagnosed on the basis of plain radiography. Dysostosis multiplex is classic in Hurler syndrome (see the images below). These findings include the following:

  • Large skull with thickened calvaria, premature suture closure, J-shaped sella turcica, and shallow orbits
  • Abnormal spacing of teeth with dentigerous cysts
  • Short, thickened and irregular clavicles
  • Short, wide, and trapezoid shaped phalanges
  • Oar-shaped ribs
  • Anterior hypoplasia of the lumbar vertebrae with kyphosis
  • Poorly formed pelvis with small femoral heads and coxa valga
  • Enlarged diaphyses of long bones and irregular metaphyses
Hurler syndrome; lateral radiograph of thoracolumb Hurler syndrome; lateral radiograph of thoracolumbar vertebrae illustrates vertebral plana. Courtesy of Bruce M. Rothschild, MD.
Hurler syndrome; widened metaphyses and diaphyses Hurler syndrome; widened metaphyses and diaphyses with truncated distal portions forming a peg characterize this radiograph. Courtesy of Bruce M. Rothschild, MD.
Hurler syndrome; widened metaphyses and diaphyses Hurler syndrome; widened metaphyses and diaphyses with truncated distal portions forming a peg characterize this radiograph. Courtesy of Bruce M. Rothschild, MD.

Computed tomography (CT) of the cranium can be used to help diagnose hydrocephalus.

Echocardiography is a useful monitoring test for ventricular function and size in MPS patients with cardiovascular disease.

Magnetic resonance imaging (MRI) is valuable for evaluation of spinal involvement in MPS VI. [16]

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Other Tests

Electroretinography is a diagnostic method to assess the presence of retinal involvement in patients with MPS.

Audiologic assessment is performed to evaluate for hearing loss in MPS.

Identification of female heterozygotes can be possible in Hunter syndrome. These females appear clinically healthy. Carrier detection is done by using hair-root analysis and single-cell cloning of fibroblast. However, these tests are not widely available at this time.

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