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I-Cell Disease (Mucolipidosis Type II) Clinical Presentation

  • Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD  more...
Updated: Aug 21, 2015


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 are as follows:[21]

  • 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.



See the list below:

  • 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.


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]

Contributor Information and Disclosures

Karl S Roth, MD Retired 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 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, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.


Margaret M McGovern, MD, PhD Professor and Chair of Pediatrics, Stony Brook University School of Medicine

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

Disclosure: Nothing to disclose.

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, Society for Inherited Metabolic Disorders

Disclosure: Nothing to disclose.

Specialty Editor Board

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 School of Medicine

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

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

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, Society for Inherited Metabolic Disorders, American Society of Gene and Cell Therapy, American Society of Human Genetics, Child Neurology Society

Disclosure: Received salary from Genzyme Corporation for management position.


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

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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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