I-Cell Disease (Mucolipidosis Type II) Workup

  • Author: Karl S Roth, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Apr 16, 2012
 

Laboratory Studies

  • Biochemical diagnosis can be made in the following 2 ways:
    • N -acetylglucosaminyl-1-phosphotransferase activity can be measured in WBCs or in cultured fibroblasts.
    • Various lysosomal enzyme activities can be measured in serum and in cultured fibroblasts. The activities of beta-hexosaminidase, iduronate sulfatase, and arylsulfatase A are deficient in cultured fibroblasts, but their serum levels are 10-20 times the reference range. Assays for lysosomal enzymes in leukocytes are not reliable because of mannose-6-phosphate–independent targeting pathways.
Next

Imaging Studies

  • Radiography
    • The characteristic bone changes are similar to those observed in the mucopolysaccharidoses.
    • The classic finding is dysostosis multiplex, with a cloaking appearance of the long tubular bones, anterior beaking and wedging of the vertebral bodies, widening of the ribs, proximal pointing of the metacarpals, and bullet-shaped phalanges.
  • Brain imaging
    • Brain imaging is not necessary to diagnose I-cell disease, although it is often performed during evaluation of developmental delay.
    • MRI and CT scan findings can be variable and nonspecific and may not aid in the diagnosis. Reported MRI and CT scan findings include completely normal scans with normal myelination, cerebral atrophy, and nonspecific white matter changes.
Previous
Next

Histologic Findings

A unique finding in I-cell disease is the presence of numerous intracytoplasmic inclusions in cells of mesenchymal origin that are observed on electron microscopy. These inclusions are membrane-bound vacuoles filled with fibrillogranular material. The contents of these vacuoles have not been well characterized; however, they appear to contain various lipids, mucopolysaccharides, and oligosaccharides.

Previous
Proceed to Treatment & Management
 
 
Contributor Information and Disclosures
Author

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.

Coauthor(s)

William B Rizzo, MD  Professor, Department of Pediatrics, University of Nebraska Medical Center

William B Rizzo, MD is a member of the following medical societies: American Society of Human Genetics and Society for Inherited Metabolic Disorders

Disclosure: Nothing to disclose.

Margaret M McGovern, MD, PhD  Professor and Chair of Pediatrics, Stony Brook University, New York

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics

Disclosure: Genzyme Grant/research funds PI

Specialty Editor Board

Edward Kaye, MD  Vice President of Clinical Research, Genzyme Corporation

Edward Kaye, MD is a member of the following medical societies: American Academy of Neurology, American Society of Gene Therapy, American Society of Human Genetics, Child Neurology Society, and Society for Inherited Metabolic Disorders

Disclosure: Genzyme Corporation Salary Management position

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Margaret M McGovern, MD, PhD  Professor and Chair of Pediatrics, Stony Brook University, New York

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics

Disclosure: Genzyme Grant/research funds PI

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, 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.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Grace Lee, MD, to the original writing and development of this article.

References

  1. Dierks T, Schlotawa L, Frese MA, Radhakrishnan K, von Figura K, Schmidt B. Molecular basis of multiple sulfatase deficiency, mucolipidosis II/III and Niemann-Pick C1 disease - Lysosomal storage disorders caused by defects of non-lysosomal proteins. Biochim Biophys Acta. Apr 2009;1793(4):710-25. [Medline].

  2. Leroy JG, DeMars RI, Opitz JM. I-cell disease. Birth Defects Orig Artic Ser. 1969;4:174-85.

  3. Spranger JW, Wiedemann HR. The genetic mucolipidoses. Diagnosis and differential diagnosis. Humangenetik. 1970;9(2):113-39. [Medline].

  4. 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].

  5. Otomo T, Higaki K, Nanba E, Ozono K, Sakai N. Lysosomal storage causes cellular dysfunction in mucolipidosis II skin fibroblasts. J Biol Chem. Oct 7 2011;286(40):35283-90. [Medline]. [Full Text].

  6. Coutinho MF, Santos LD, Girisha KM, Satyamoorthy K, Lacerda L, Prata MJ, et al. Mucolipidosis type II a/ß with a homozygous missense mutation in the GNPTAB gene. Am J Med Genet A. Apr 11 2012;[Medline].

  7. Krivan G, Timar L, Goda V, et al. Bone marrow transplantation in non-malignant disorders. Bone Marrow Transplant. Dec 1998;22 Suppl 4:S80-3. [Medline].

  8. Bocca G, Monnens LA. Defective proximal tubular function in a patient with I-cell disease. Pediatr Nephrol. Aug 2003;18(8):830-2. [Medline].

  9. Breningstall GN, Tubman DE. Magnetic resonance imaging in a patient with I-cell disease. Clin Neurol Neurosurg. May 1994;96(2):161-3. [Medline].

  10. Goodman ML, Pang D. Spinal cord injury in I-cell disease. Pediatr Neurosci. 1988;14(6):315-8. [Medline].

  11. Gopaul KP, Crook MA. The inborn errors of sialic acid metabolism and their laboratory investigation. Clin Lab. 2006;52(3-4):155-69. [Medline].

  12. Kawashima I, Ohsawa M, Fukushige et al. Cytochemical analysis of storage materials in cultured skin fibroblasts from patients with I-cell disease. Clin Chim Acta. Mar 2007;378(1-2):142-6. [Medline].

  13. Kornfeld S, Sly WS. I-cell disease and pseudo-Hurler polydystrophy: disorders of lysosomal enzyme phosphorylation and localization. Metab Mol Bases Inherited Dis. 2001;3:3469-82.

  14. Kudo M, Brem MS, Canfield WM. Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha / beta -subunits precursor gene. Am J Hum Genet. Mar 2006;78(3):451-63. [Medline].

  15. Leroy JG, Martin JJ. Mucolipidosis II (I-cell disease): present status of knowledge. Birth Defects Orig Artic Ser. 1975;DA - 19760301(6):283-93. [Medline].

  16. Leroy JG, Spranger JW, Feingold M, Opitz JM, Crocker AC. I-cell disease: a clinical picture. J Pediatr. Sep 1971;79(3):360-5. [Medline].

  17. Tiede S, Storch S, Lubke T, et al. Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase. Nat Med. Oct 2005;11(10):1109-12. [Medline].

 
Previous
Next
 
Profile view of 3-year-old with I-cell disease. Growth ceased more than one year earlier. Note small orbits, proptotic eyes, full and prominent mouth caused by gingival hypertrophy, short and broad hands, stiffening of small hand joints, prominent abdomen with umbilical hernia, and limited extension of the hips and knees.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.