eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Mucopolysaccharidosis Type VI: Differential Diagnoses & Workup

Author: Paul R Harmatz, MD, Attending Physician, Department of Gastroenterology and Nutrition, Children's Hospital Oakland
Coauthor(s): Margaret McGovern, MD, PhD, Vice Chair, Professor, Department of Human Genetics, Mount Sinai School of Medicine
Contributor Information and Disclosures

Updated: Dec 11, 2008

Differential Diagnoses

Mucopolysaccharidoses Type VII
Mucopolysaccharidosis Type VII
Mucopolysaccharidosis Type I H/S
Multiple Sulfatase Deficiency
Mucopolysaccharidosis Type IH
Mucopolysaccharidosis Type II
Mucopolysaccharidosis Type IS

Other Problems to Be Considered

Mucolipidoses

Workup

Laboratory Studies

  • Urine glycosaminoglycan analysis can be performed using various qualitative or quantitative methods. These studies are useful for establishing the likely diagnosis of mucopolysaccharidosis (MPS) but do not provide a specific diagnosis, which requires enzymatic testing.
  • Definitive diagnosis requires the determination of the specific lysosomal enzyme level in cultured fibroblasts or isolated leukocytes.
  • Normal levels of a second sulfatase should be documented to exclude multiple sulfatase deficiency.

Imaging Studies

  • Perform skeletal survey studies to reveal dysostosis multiplex. Findings may include the following:
    • Macrocephaly with an enlarged sella
    • Acetabulum hypoplasia
    • Ovoid deformities of the vertebrae
    • Anterior hypoplasia of the L1 and L2 vertebral bodies
    • Epiphyseal dysplasia of the proximal femur
    • Evidence of kyphoscoliosis
  • Echocardiography can reveal valvular heart disease, which is common. Acute infantile cardiomyopathy has also been reported in mucopolysaccharidosis type VI (MPS VI).
  • MRI of the brain and spine may demonstrate hydrocephalus or provide evidence for spinal cord compression, especially in the cervical region.
  • Flexion-extension radiography of the C-spine may demonstrate atlantoaxial instability and subluxation of C1 on C2.

Other Tests

  • Perform an audiological evaluation because deafness and hearing loss are common in MPS.
  • Perform an ophthalmologic examination to identify corneal opacities, vision change, and optic nerve abnormalities, suggesting increased intracranial pressure.
  • Perform pulmonary function tests to monitor restrictive and obstructive disease and perform a sleep study to evaluate for sleep apnea.

Histologic Findings

  • Lysosomal engorgement in tissue biopsies is evident, as are vacuolated lymphocytes on peripheral blood smear.

Staging

  • Urine glycosaminoglycan (GAG) level corrected for creatinine is a biochemical disease marker that can provide a crude estimate of disease severity and response to specific treatment (bone marrow transplantation [BMT] or enzyme replacement therapy).

More on Mucopolysaccharidosis Type VI

Overview: Mucopolysaccharidosis Type VI
Differential Diagnoses & Workup: Mucopolysaccharidosis Type VI
Treatment & Medication: Mucopolysaccharidosis Type VI
Follow-up: Mucopolysaccharidosis Type VI
References
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References

  1. Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA. Jan 20 1999;281(3):249-54. [Medline].

  2. Baehner F, Schmiedeskamp C, Krummenauer F, et al. Cumulative incidence rates of the mucopolysaccharidoses in Germany. J Inherit Metab Dis. 2005;28(6):1011-7. [Medline].

  3. Pinto R, Caseiro C, Lemos M, et al. Prevalence of lysosomal storage diseases in Portugal. Eur J Hum Genet. Feb 2004;12(2):87-92. [Medline].

  4. Bagewadi S, Roberts J, Mercer J, Jones S, Stephenson J, Wraith JE. Home treatment with Elaprase and Naglazyme is safe in patients with mucopolysaccharidoses types II and VI, respectively. J Inherit Metab Dis. Dec 2008;31(6):733-7. [Medline].

  5. Harmatz P, Giugliani R, Schwartz I. Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-. J Pediatr. Apr 2006;148(4):533-539. [Medline].

  6. Harmatz P, Kramer WG, Hopwood JJ, et al. Pharmacokinetic profile of recombinant human N-acetylgalactosamine 4-sulphatase enzyme replacement therapy in patients with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): a phase I/II study. Acta Paediatr Suppl. Mar 2005;94(447):61-8; discussion 57. [Medline].

  7. Isbrandt D, Arlt G, Brooks DA, Hopwood JJ, et al. Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): six unique arylsulfatase B gene alleles causing variable disease phenotypes. Am J Hum Genet. Mar 1994;54(3):454-63. [Medline].

  8. Jones KL. Smith's Recognizable Patterns of Human Malformation. 1997:468-9.

  9. Karageorgos L, Harmatz P, Simon J. Mutational analysis of mucopolysaccharidosis type VI patients undergoing a trial of enzyme replacement therapy. Hum Mutat. Mar 2004;23(3):229-33. [Medline].

  10. Krivit W. Stem cell bone marrow transplantation in patients with metabolic storage diseases. Adv Pediatr. 2002;49:359-78. [Medline].

  11. Nelson J, Crowhurst J, Carey B, Greed L. Incidence of the mucopolysaccharidoses in Western Australia. Am J Med Genet A. Dec 15 2003;123(3):310-3. [Medline].

  12. Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: The Metabolic and Molecular Bases of Inherited Disease. 1995:2465-94.

  13. O'Brien JF, Cantz M, Spranger J. Maroteaux-Lamy disease (mucopolysaccharidosis VI), subtype A: deficiency of a N-acetylgalactosamine-4-sulfatase. Biochem Biophys Res Commun. Oct 8 1974;60(3):1170-7. [Medline].

  14. Poorthuis BJ, Wevers RA, Kleijer WJ, et al. The frequency of lysosomal storage diseases in The Netherlands. Hum Genet. Jul-Aug 1999;105(1-2):151-6. [Medline].

  15. Swiedler SJ, Beck M, Bajbouj M. Threshold effect of urinary glycosaminoglycans and the walk test as indicators of disease progression in a survey of subjects with Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). Am J Med Genet A. Apr 15 2005;134(2):144-50. [Medline].

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Further Reading

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Keywords

Maroteaux-Lamy syndrome, mucopolysaccharidosis type VI, arylsulfatase B deficiency, polydystrophic dwarfism, type VI mucopolysaccharidosis, MPS, MPS VI, coarse facies, corneal clouding, organomegaly, joint stiffness, dysostosis multiplex, hernias, short stature, mental retardation, otitis media, hearing loss, chronic respiratory tract infections, sleep apnea, pulmonary hypertension, hydrocephalus, rapid-onset blindness, cardiac valve insufficiency, dwarfism, hepatosplenomegaly, macrocephaly, claw-hand deformities, hirsutism

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Contributor Information and Disclosures

Author

Paul R Harmatz, MD, Attending Physician, Department of Gastroenterology and Nutrition, Children's Hospital Oakland
Paul R Harmatz, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, American Society of Hematology, American Society of Human Genetics, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: BioMarin Pharmaceutical Inc. Consulting fee Consulting; BioMarin Pharmaceutical Inc. Honoraria Speaking and teaching

Coauthor(s)

Margaret McGovern, MD, PhD, Vice Chair, Professor, Department of Human Genetics, Mount Sinai School of Medicine
Margaret McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics
Disclosure: Nothing to disclose.

Medical Editor

Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Clinical Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Margaret McGovern, MD, PhD, Vice Chair, Professor, Department of Human Genetics, Mount Sinai School of Medicine
Margaret McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting; Pfizer Honoraria Consulting

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
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