I-Cell Disease (Mucolipidosis Type II) Clinical Presentation

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

History

Developmental delay and growth failure are common presentations of I-cell disease. Psychomotor deterioration is rapid and progressive. Some physical signs, such as hip dislocations, inguinal hernias, hepatomegaly, joint limitation, and skin changes, may be present at birth. Coarse facial features and skeletal abnormalities become more conspicuous with time. The full clinical picture is usually evident by the first year of life.

  • Growth failure and failure to thrive are rapidly progressive.
    • Birth weight and length may be decreased.
    • Linear growth decelerates during the first year of life and ceases by age 2 years.
    • Head circumference is usually preserved.
  • Developmental delay is severe and is often the presenting symptom.
    • Infants smile and follow and grasp objects but are unable to roll over or support their weight with their legs.
    • Generalized hypotonia and poor head control are observed.
    • Motor delay is usually more severe than cognitive delay.
    • The severity of developmental delay widely varies.
  • Coarse facial features
    • The characteristic facies is similar to that observed in Hurler syndrome.
    • Gingival hypertrophy is a distinguishing feature.
  • Radiographic findings
    • These findings are similar to those observed in Hurler syndrome, a condition with which I-cell disease may be confused.
    • In early infancy, periosteal new-bone formation leads to cloaking of the long bones.
    • The tubular bones of the upper extremities are short and widened, and the phalanges are bullet-shaped.
    • Anterior beaking and wedging of the vertebrae occur. This results in a lumbar gibbus deformity and kyphoscoliosis.
    • Widening of the ribs is observed.
  • Frequent upper respiratory tract infections: These patients experience recurrent bouts of pneumonia, bronchitis, and otitis media.
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Physical

  • Coarse facial features
    • High, narrow forehead
    • Puffy eyelids, epicanthal folds
    • Flat nasal bridge, anteverted nares
    • Long philtrum
    • Prominent gingival hyperplasia and macroglossia
  • Musculoskeletal abnormalities
    • Congenital hip dislocation
    • Joint stiffness and claw hand deformities
    • Lumbar gibbus deformity and kyphoscoliosis
  • Abdomen
    • Umbilical and inguinal hernias
    • Diastasis recti
    • Mild hepatomegaly
  • Cardiovascular findings: Aortic insufficiency murmur may be present
  • Ophthalmologic findings: Corneas may be clear or hazy.
  • Neurologic findings: Generalized hypotonia may be observed.
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Causes

  • I-cell disease is an autosomal-recessive disorder caused by a deficiency of the enzyme UDP-N -acetylglucosamine: N -acetylglucosaminyl-1-phosphotransferase. Deficiency of this phosphotransferase prevents the addition of the mannose-6-phosphate recognition marker because the lysosomal enzymes are modified in the Golgi apparatus before being transported to the lysosome; therefore, lysosomal enzymes cannot be endocytosed into the lysosome for normal processing and use.[5]
  • The UDP-N -acetylglucosamine: N -acetylglucosaminyl-1-phosphotransferase enzyme is the product of the GNPTA gene, which has been mapped to chromosome band 4q21-q23. Various mutations in this gene have been reported in patients with I-cell disease.[6]
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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].

 
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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.
 
 
 
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