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 [MPS II]) 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 [10, 19] :
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Enzyme deficiency - Alpha-L-iduronidase
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Urinary glycosaminoglycan (GAG) - Dermatan sulfate, heparan sulfate
Assays for MPS I-H/S (Hurler-Scheie syndrome) are as follows:
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Enzyme deficiency - Alpha-L-iduronidase
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Urinary GAG - Dermatan sulfate, heparan sulfate
Assays for MPS IS (Scheie syndrome) are as follows:
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Enzyme deficiency - Alpha-L-iduronidase
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Urinary GAG - Dermatan sulfate, heparan sulfate
Assays for MPS II-A (Hunter syndrome, severe) [11] are as follows:
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Enzyme deficiency - Iduronate sulfatase
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Urinary GAG - Dermatan sulfate, heparan sulfate
Assays for MPS II-B (Hunter syndrome, mild) [11] are as follows:
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Enzyme deficiency - Iduronate sulfatase
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Urinary GAG - Dermatan sulfate, heparan sulfate
Assays for MPS III-A (Sanfilippo syndrome A) are as follows:
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Enzyme deficiency - Heparan N-sulfatase
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Urinary GAG - Heparan sulfate
Assays for MPS III-B (Sanfilippo syndrome B) are as follows:
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Enzyme deficiency - N-acetylglucosaminidase
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Urinary GAG - Heparan sulfate
Assays for MPS III-C (Sanfilippo syndrome C) are as follows:
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Enzyme deficiency - Acetyl-coenzyme A: Alpha-glucosamine- N-acetyltransferase
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Urinary GAG - Heparan sulfate
Assays for MPS III-D (Sanfilippo syndrome D) are as follows:
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Enzyme deficiency - N-acetyl alpha-glucosamine-6-sulfatase
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Urinary GAG - Heparan sulfate
Assays for MPS IV-A (Morquio syndrome A) are as follows:
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Enzyme deficiency - N-acetylgalactosamine-6-sulfatase
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Urinary GAG - Keratan sulfate
Assays for MPS IV-B (Morquio syndrome B) are as follows:
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Enzyme deficiency - B-galactosidase
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Urinary GAG - Keratan sulfate
Assays for MPS VI (Maroteaux-Lamy syndrome) are as follows:
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Enzyme deficiency - N-acetylgalactosamine-4-sulfatase
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Urinary GAG - Dermatan sulfate
Assays for MPS VII (Sly syndrome) are as follows:
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Enzyme deficiency - B-glucuronidase
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Urinary GAG - Dermatan sulfate, heparan sulfate
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:
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Large skull with thickened calvaria, premature suture closure, J-shaped sella turcica, and shallow orbits
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Abnormal spacing of teeth with dentigerous cysts
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Short, thickened and irregular clavicles
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Short, wide, and trapezoid shaped phalanges
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Oar-shaped ribs
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Anterior hypoplasia of the lumbar vertebrae with kyphosis
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Poorly formed pelvis with small femoral heads and coxa valga
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Enlarged diaphyses of long bones and irregular metaphyses
Hurler syndrome; lateral radiograph of thoracolumbar vertebrae illustrates vertebral plana. Courtesy of Bruce M. Rothschild, MD.
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 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. [20] A study by Kovac et al found that quantitative MRI was able to detect differences in brain macrostructure in patients with severe or attenuated MPS I, as well as to distinguish between the two forms. [21]
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 (MPS II). 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.
A study by Aboulnasr et al found quantitative determination of heparan sulfate and dermatan sulfate by means of mass spectrometry to be useful for antenatal diagnosis of MPS II. [22]
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An 8-year-old boy with Morquio syndrome and severe kyphoscoliosis. Courtesy of Dennis P. Grogan, MD.
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A 7-year-old girl with Morquio syndrome and typical severe genu valgum. Courtesy of Dennis P. Grogan, MD.
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Morquio syndrome; widened bases of phalanges with osteopenia. Courtesy of Bruce M. Rothschild, MD.
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Morquio syndrome; lateral radiograph of thoracolumbar vertebrae illustrates vertebral body beaking. Courtesy of Bruce M. Rothschild, MD.
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Hurler syndrome; lateral radiograph of thoracolumbar vertebrae illustrates vertebral plana. Courtesy of Bruce M. Rothschild, MD.
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Morquio syndrome; anteroposterior radiograph of pelvis illustrates avascular necrosis of femoral head. Courtesy of Bruce M. Rothschild, MD.
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Hurler syndrome; widened metaphyses and diaphyses with truncated distal portions forming a peg characterize this radiograph. Courtesy of Bruce M. Rothschild, MD.
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Hurler syndrome; widened metaphyses and diaphyses with truncated distal portions forming a peg characterize this radiograph. Courtesy of Bruce M. Rothschild, MD.
