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Mucopolysaccharidosis Workup

  • Author: Tarek Bittar, MD; Chief Editor: Jeffrey D Thomson, MD  more...
 
Updated: Feb 02, 2016
 

Laboratory Studies

Prenatal screening

Chorionic villus sampling is performed around the ninth week 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[6, 14] :

  • 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)[7]  are as follows:

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

Assays for MPS II-B (Hunter syndrome, mild)[7]  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.

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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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Contributor Information and Disclosures
Author

Tarek Bittar, MD Staff Physician, Department of Orthopedic Surgery, Martin Luther King Medical Center

Tarek Bittar, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons

Disclosure: Nothing to disclose.

Coauthor(s)

Eleby R Washington, III, MD, FACS Associate Professor, Department of Surgery, Division of Orthopedics, Charles R Drew University of Medicine and Science

Eleby R Washington, III, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, American Medical Association, International College of Surgeons, National Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

George H Thompson, MD Director of Pediatric Orthopedic Surgery, Rainbow Babies and Children’s Hospital, University Hospitals Case Medical Center, and MetroHealth Medical Center; Professor of Orthopedic Surgery and Pediatrics, Case Western Reserve University School of Medicine

George H Thompson, MD is a member of the following medical societies: American Orthopaedic Association, Scoliosis Research Society, Pediatric Orthopaedic Society of North America, American Academy of Orthopaedic Surgeons

Disclosure: Received none from OrthoPediatrics for consulting; Received salary from Journal of Pediatric Orthopaedics for management position; Received none from SpineForm for consulting; Received none from SICOT for board membership.

Chief Editor

Jeffrey D Thomson, MD Associate Professor, Department of Orthopedic Surgery, University of Connecticut School of Medicine; Director of Orthopedic Surgery, Department of Pediatric Orthopedic Surgery, Associate Director of Clinical Affairs for the Department of Surgical Subspecialties, Connecticut Children’s Medical Center; President, Connecticut Children's Specialty Group

Jeffrey D Thomson, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons

Disclosure: Nothing to disclose.

Additional Contributors

Charles T Mehlman, DO, MPH Professor of Pediatrics and Pediatric Orthopedic Surgery, Division of Pediatric Orthopedic Surgery, Director, Musculoskeletal Outcomes Research, Cincinnati Children's Hospital Medical Center

Charles T Mehlman, DO, MPH is a member of the following medical societies: American Academy of Pediatrics, American Fracture Association, Scoliosis Research Society, Pediatric Orthopaedic Society of North America, American Medical Association, American Orthopaedic Foot and Ankle Society, American Osteopathic Association, Arthroscopy Association of North America, North American Spine Society, Ohio State Medical Association

Disclosure: Nothing to disclose.

References
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An 8-year-old boy with Morquio syndrome and severe kyphoscoliosis. Courtesy of Dennis P. Grogan, MD.
A 7-year-old girl with Morquio syndrome and typical severe genu valgum. Courtesy of Dennis P. Grogan, MD.
Morquio syndrome; widened bases of phalanges with osteopenia. Courtesy of Bruce M. Rothschild, MD.
Morquio syndrome; lateral radiograph of thoracolumbar vertebrae illustrates vertebral body beaking. Courtesy of Bruce M. Rothschild, MD.
Hurler syndrome; lateral radiograph of thoracolumbar vertebrae illustrates vertebral plana. Courtesy of Bruce M. Rothschild, MD.
Morquio syndrome; anteroposterior radiograph of pelvis illustrates avascular necrosis of femoral head. 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.
 
 
 
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