Mucopolysaccharidosis Workup

  • Author: Tarek Bittar, MD; Chief Editor: Dennis P Grogan, MD   more...
 
Updated: May 21, 2012
 

Laboratory Studies

  • Prenatal screening
    • Chorionic villus sampling: This test is performed around the ninth week of pregnancy and has become increasingly popular for the diagnosis of MPS.
    • Amniocentesis: Prenatal 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 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.
    • MPS IH (Hurler syndrome)[6, 10]
      • Enzyme deficiency - Alpha-L-Iduronidase
      • Urinary glycosaminoglycan (GAG) - Dermatan sulfate, heparan sulfate
    • MPS I-H/S (Hurler-Scheie syndrome)
      • Enzyme deficiency - Alpha-L-Iduronidase
      • Urinary GAG - Dermatan sulfate, heparan sulfate
    • MPS IS (Scheie syndrome)
      • Enzyme deficiency - Alpha-L-Iduronidase
      • Urinary GAG - Dermatan sulfate, heparan sulfate
    • MPS II-A (Hunter syndrome, severe)[7]
      • Enzyme deficiency - Iduronate sulfatase
      • Urinary GAG - Dermatan sulfate, heparan sulfate
    • MPS II-B (Hunter syndrome, mild)[7]
      • Enzyme deficiency - Iduronate sulfatase
      • Urinary GAG - Dermatan sulfate, heparan sulfate
    • MPS III-A (Sanfilippo syndrome A)
      • Enzyme deficiency - Heparan N -sulfatase
      • Urinary GAG - Heparan sulfate
    • MPS III-B (Sanfilippo syndrome B)
      • Enzyme deficiency -N -acetylglucosaminidase
      • Urinary GAG - Heparan sulfate
    • MPS III-C (Sanfilippo syndrome C)
      • Enzyme deficiency - Acetyl-coenzyme A: Alpha-glucosamine-N -acetyltransferase
      • Urinary GAG - Heparan sulfate
    • MPS III-D (Sanfilippo syndrome D)
      • Enzyme deficiency -N -acetyl alpha-glucosamine-6-sulfatase
      • Urinary GAG - Heparan sulfate
    • MPS IV-A (Morquio syndrome A)
      • Enzyme deficiency: N -acetylgalactosamine-6-sulfatase
      • Urinary GAG: Keratan sulfate
    • MPS IV-B (Morquio syndrome B)
      • Enzyme deficiency - B-galactosidase
      • Urinary GAG - Keratan sulfate
    • MPS VI (Maroteaux-Lamy)
      • Enzyme deficiency -N -acetylgalactosamine-4-sulfatase
      • Urinary GAG - Dermatan sulfate
    • MPS VII (Sly syndrome)
      • Enzyme deficiency - B-glucuronidase
      • Urinary GAG - Dermatan sulfate, heparan sulfate
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Imaging Studies

  • Radiographs: Dysostosis multiplex refers to a constellation of skeletal abnormalities in MPS conditions diagnosed based on plain radiographs. 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 metaphysesHurler syndrome; lateral radiograph of thoracolumbHurler 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.
  • CT scan of the cranium: This can be used to help diagnose hydrocephalus.
  • Echocardiogram: This 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.
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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, and National Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

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, 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, Pediatric Orthopaedic Society of North America, and Scoliosis Research Society

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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 Academy of Orthopaedic Surgeons, American Orthopaedic Association, Pediatric Orthopaedic Society of North America, and Scoliosis Research Society

Disclosure: OrthoPediatrics None Consulting; Journal of Pediatric Orthopaedics Salary Management position; SpineForm None Consulting; SICOT None Board membership

Dinesh Patel, MD, FACS  Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital

Dinesh Patel, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons

Disclosure: Nothing to disclose.

Chief Editor

Dennis P Grogan, MD  Clinical Professor, Department of Orthopedic Surgery, University of South Florida College of Medicine; Chief of Staff, Department of Orthopedic Surgery, Shriners Hospital for Children of Tampa

Dennis P Grogan, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Medical Association, American Orthopaedic Association, American Orthopaedic Foot and Ankle Society, Eastern Orthopaedic Association, Irish American Orthopaedic Society, Pediatric Orthopaedic Society of North America, and Scoliosis Research Society

Disclosure: Nothing to disclose.

References

  1. Bassyouni HT, Afifi HH, el-Awadi MK. Mucopolysaccharidosis type I: clinical and biochemical study. East Mediterr Health J. Mar-May 2000;6(2-3):359-66. [Medline].

  2. Jones KL. Storage disorders. In: Smith's Recognizable Patterns of Human Malformation. Philadelphia, Pa: WB Saunders Co; 1997:456-471.

  3. Muenzer J. Mucopolysaccharidoses. Adv Pediatr. 1986;33:269-302. [Medline].

  4. Tandon V, Williamson JB, Cowie RA. Spinal problems in mucopolysaccharidosis I (Hurler syndrome). J Bone Joint Surg Br. Nov 1996;78(6):938-44. [Medline].

  5. Masterson EL, Murphy PG, O'Meara A, Moore DP, Dowling FE, Fogarty EE. Hip dysplasia in Hurler's syndrome: orthopaedic management after bone marrow transplantation. J Pediatr Orthop. Nov-Dec 1996;16(6):731-3. [Medline].

  6. Dupont C, Hachem CE, Harchaoui S, Ribault V, Amiour M, Guillot M. [Hurler syndrome: Early diagnosis and successful enzyme replacement therapy: A new therapeutic approach. Case report.]. Arch Pediatr. Jan 2008;15(1):45-49. [Medline].

  7. Martin R, Beck M, Eng C, Giugliani R, Harmatz P, Muñoz V. Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome). Pediatrics. Feb 2008;121(2):e377-86. [Medline].

  8. Wraith JE, Scarpa M, Beck M, Bodamer OA, De Meirleir L, Guffon N. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. Mar 2008;167(3):267-277. [Medline].

  9. Menkès CJ, Rondot P. Idiopathic osteonecrosis of femur in adult Morquio type B disease. J Rheumatol. Nov 2007;34(11):2314-6. [Medline].

  10. Tolar J, Grewal SS, Bjoraker KJ, Whitley CB, Shapiro EG, Charnas L. Combination of enzyme replacement and hematopoietic stem cell transplantation as therapy for Hurler syndrome. Bone Marrow Transplant. Nov 26 2007;[Medline].

  11. Chan YL, Lin SP, Man TT. Clinical experience in anesthetic management for children with mucopolysaccharidoses: Report of ten cases. Acta Paediatr Taiwan. Sep-Oct 2001;42(5):306-8. [Medline].

  12. Tomatsu S, Montaño AM, Ohashi A, Oikawa H, Oguma T, Dung VC. Enzyme replacement therapy in a murine model of Morquio A syndrome. Hum Mol Genet. Dec 3 2007;[Medline].

  13. Guffon N, Souillet G, Maire I, et al. Follow-up of nine patients with Hurler syndrome after bone marrow transplantation. J Pediatr. Jul 1998;133(1):119-25. [Medline].

  14. Clarke LA. Idursulfase for the treatment of mucopolysaccharidosis II. Expert Opin Pharmacother. Feb 2008;9(2):311-7. [Medline].

  15. Arn P, Whitley C, Wraith JE, Webb HW, Underhill L, Rangachari L, et al. High rate of postoperative mortality in patients with mucopolysaccharidosis I: findings from the MPS I Registry. J Pediatr Surg. Mar 2012;47(3):477-84. [Medline].

  16. Kasper DC, Iqbal F, Dvorakova L, Zeman J, Magner M, Bodamer O, et al. Rapid and accurate denaturating high performance liquid chromatography protocol for the detection of alpha-l-iduronidase mutations causing mucopolysaccharidosis type I. Clin Chim Acta. Mar 2010;411(5-6):345-50. [Medline].

  17. Kottler U, Demir D, Schmidtmann I, Beck M, Pitz S. Central Corneal Thickness in Mucopolysaccharidosis II and VI. Cornea. Mar 2010;29(3):260-2. [Medline].

 
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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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