• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
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  • Standard Therapies
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I Cell Disease


Last updated: September 17, 2007
Years published: 1988, 1989, 1996, 2003, 2007

Disease Overview

I-cell disease (mucolipidosis II) is a rare inherited metabolic disorder characterized by coarse facial features, skeletal abnormalities and mental retardation. The symptoms of I-cell disease are similar to but more severe than those of Hurler syndrome. The symptoms associated with this disorder typically become obvious during infancy and may include multiple abnormalities of the skull and face and growth delays.

This disorder belongs to a group of diseases known as lysosomal storage disorders. Lysosomes are particles bound in membranes within cells that break down certain fats and carbohydrates. Multiple enzyme deficiencies associated with I-cell disease lead to the accumulation of certain fatty substances (mucolipids) and certain complex carbohydrates (mucopolysaccharides) within the cells of many tissues of the body.

I-cell disease is caused by a mutation in the GNPTA gene that leads to a deficiency in the enzyme UDP-N-acetylglucoseamine-1-phosphotransferase. I-cell disease is inherited as an autosomal recessive genetic trait.

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  • Inclusion Cell Disease
  • Leroy Disease
  • ML Disorder, Type II
  • ML II
  • Mucolipidosis II
  • N-Acetylglucosamine-1-Phosphotransferase Deficiency
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Signs & Symptoms

Some of the physical features associated with I-cell disease (ML II) may be apparent at birth (congenital), whereas other features may become apparent between the ages of 6 to 10 months. Craniofacial abnormalities may include coarse facial features, a depressed nasal bridge, a long and narrow head, an unusually high and narrow forehead, and/or skin folds on the inner corners of the eyes (epicanthal folds). The skin may appear to be unusually thick and tight in certain areas of the body (e.g., face, arms, and legs). The corneas of the eyes may appear cloudy.

Infants with I-cell disease may also have skeletal malformations including abnormal curvature of the spine from side to side (scoliosis) and/or from front to back (kyphosis), an unusually short neck, dislocation of the hip at birth (congenital), swelling or enlargement of the top portion of the spine (lumbar gibbus), and/or limited mobility of the shoulders. Skeletal abnormalities may also include misaligned bones in the spinal column (vertebral breaking and wedging), wider than normal spaces between ribs, and/or unusual positioning of the fingers (metacarpal pointing). On occasion, infants with I-cell disease may have fingers that are fused together (split hand deformity or ectrodactyly). (For more information on this disorder, choose “split hand” as your search term in the Rare Disease Database.)

Children with I-cell disease typically have severe delays in the development of gross and fine motor skills, hearing loss, lack of muscle tone (hypotonia), and varying degrees of mental retardation. Growth delays usually result in short stature (dwarfism). In some children with this disorder, a portion of the intestines may protrude through an abnormal opening in the abdominal wall in the area of the navel (umbilical hernia) and/or the groin (inguinal hernia). Abnormal enlargement of the liver (hepatomegaly), is often observed in association with a protruding abdomen in infants with I-cell disease.

Other symptoms of I-cell disease may include frequent respiratory infections, constipation and/or diarrhea, overgrowth of gum tissue (gingival hyperplasia), and/or joint stiffness or joints that are “frozen” in place (contractures). Some children with I-cell disease may have abnormalities of the heart such as defects of the heart valves, enlargement of the heart (cardiomegaly), congestive heart failure and/or heart murmurs.

Individuals with I-cell disease often die in childhood, although some patients survive into their teens.

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I-cell disease (Mucolipidosis II) is caused by a mutation in the GNPTA gene that is located on the long arm of chromosome 4 (4q21-q23).

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 4q21” refers to band 21 on the long arm of chromosome 4. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

The GNPTA gene mutation leads to a deficiency in the enzyme UDP-N-acetylglucoseamine-1-phosphotransferase that is involved in the synthesis of mannose-6-phosphate, resulting in decreased intracellular levels of lysosomal enzymes and increased levels in blood serum and body fluid. The symptoms of I-cell disease develop due to deficiencies of a variety of lysosomal enzymes in the cells of the body causing an abnormal accumulation of certain fatty substances (mucolipids) and certain complex carbohydrates (mucopolysaccharides) within the cells of many tissues of the body.

I-cell disease is inherited as an autosomal recessive genetic trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

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Affected populations

I-Cell Disease is a rare disorder that affects males and females in equal numbers. Siblings of affected infants have a 1 in 4 chance of being affected by this disorder. Approximately 30 cases of I-Cell Disease have been reported in the medical literature. This disease appears to be more common in Japan than in other countries.

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I-cell disease can be diagnosed before birth (prenatally) utilizing amniocentesis or chorionic villus sampling. Amniocentesis is a procedure in which a small portion of the fluid that surrounds the fetus (amniotic fluid) is removed and cells from the fluid are then tested in the laboratory. Chorionic villus sampling (CVS) is a prenatal diagnostic procedure in which a small sample of tissue is removed from the placenta. Abnormally low levels of UDP-N-acetylglucoseamine-1-phosphotransferase enzyme activity in amniotic fluid cells or chorionic villi suggest the diagnosis of I-cell disease.

The diagnosis of I-cell disease may be confirmed in an infant by a thorough clinical evaluation, patient history, and specialized laboratory testing. UDP-N-acetylglucoseamine-1-phosphotransferase enzyme activity can be measured in white blood cells or in cultured fibroblasts. Lysosomal enzymes are typically elevated in the blood serum and decreased in cultured fibroblasts.

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Standard Therapies


The treatment of I-cell disease is symptomatic and supportive. Antibiotics are often prescribed for respiratory infections and yearly flu shots are important. Physical therapy is encouraged to maintain joint function and mobility as long as possible. Total hip replacement has been most effective when performed after puberty. Other orthopedic complications may be managed as they arise. Hearing aids should be considered. Sleep studies can determine the degree of obstructive sleep apnea and the need for treatment. In some cases, heart problems may be treated surgically.

Genetic counseling is advised for families who have a child with this disorder.

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Clinical Trials and Studies

Experimental therapies are aimed at treating I-cell disease as early as possible. Bone marrow replacement transplantation has been attempted for the treatment of this disorder but the benefit was limited.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:


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Muenzer J and Wedehase B. Mucolipidosis ll and lll. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003:472-473.

Kornfeld S, Sly WS, I-cell and pseudo-Hurler polydystrophy: disorders of lysosomal enzyme phosphorylation and localization. In: Scriver CR, Beaudet AL, Sly WS, et al, eds. The Metabolic and Molecular Basis of Inherited Disease, 7th ed. New York: McGraw-Hill, 1995:2495-2508.

Buyse ML, ed. Birth Defects Encyclopedia. Blackwell Scientific Publications, 1990:1157-58.

Wyngaarden JB and Smith LH. Cecil Textbook of Medicine, 19th ed. W.B. Saunders Co. 1992:1121.


Beck M, Barone R, et al. Inter-and intrafamilial variability in mucolipidosis ll (I-cell disease). Clin Genet 1995;47;191-200.

Pazzaglia UE, et al. Study of bone pathology in early mucolipidosis ll (I-cell disease). Eur J Pediatr 1989;148(6):553-57.

Pazzaglia UE, et al. Mucolipidosis ll: Correlation between radiological features and histopathology of the bones. Pedatr Radio 1989;19(6-7):406-13.

Poenaru L, et al. Prenatal diagnosis of mucolipidosis type ll on first-trimester amniotic fluid. Prenat Diagn 1990;10(4):231-35.


McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry No. 252500; Last Update: 5/30/03.

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