eMedicine Specialties > Orthopedic Surgery > Pediatrics

Mucopolysaccharidosis: Differential Diagnoses & Workup

Author: Tarek Bittar, MD, Staff Physician, Department of Orthopedic Surgery, Martin Luther King Medical Center
Coauthor(s): Eleby R Washington III, MD, FACS, Associate Professor, Department of Surgery, Division of Orthopedics, Charles R Drew University of Medicine and Science
Contributor Information and Disclosures

Updated: Mar 4, 2008

Differential Diagnoses

Other Problems to Be Considered

Morquio syndrome can be confused with spondyloepiphyseal dysplasia, which is a severe form of skeletal dysplasia. In fact, many skeletal dysplasias were falsely labeled as Morquio syndrome until the discovery in the early 1960s that Morquio syndrome is a lysosomal storage disease.

Workup

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

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 Images 5, 7-8). 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
  • 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.

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.

More on Mucopolysaccharidosis

Overview: Mucopolysaccharidosis
Differential Diagnoses & Workup: Mucopolysaccharidosis
Treatment & Medication: Mucopolysaccharidosis
Follow-up: Mucopolysaccharidosis
Multimedia: Mucopolysaccharidosis
References
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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, et al. 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].

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Further Reading

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Keywords

MPS, inherited metabolic disorders, lysosomal enzyme deficiency, lysosomal storage disease, Hurler syndrome, MPS IH, Hurler-Scheie syndrome, MPS I-H/S, Scheie syndrome, MPS IS, Hunter syndrome, MPS II, Sanfilippo syndrome, MPS III, Morquio syndrome, MP IV, Maroteaux-Lamy syndrome, MPS VI, Sly syndrome, MPS VII

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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.

Medical Editor

Charles T Mehlman, DO, MPH, Director, Musculoskeletal Outcomes Research, Associate Professor, Division of Pediatric Orthopaedic Surgery, 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 Oncology Group, and Scoliosis Research Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

George H Thompson, MD, Professor of Orthopedic Surgery and Pediatrics, Department of Pediatric Orthopedic Surgery, Case Western Reserve University; Director, Rainbow Babies and Children's Hospital
George H Thompson, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Orthopaedic Surgeons, American Academy of Pediatrics, and Ohio State Medical Association
Disclosure: Nothing to disclose.

CME Editor

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, American Association of Physicians of Indian Origin, American College of International Physicians, and American College of 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.

 
 
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