What is I-Cell disease?

I-Cell disease is also known as Mucolipidosis II (ML II). It is an inherited disorder that is part of a larger group of disorders called Lysosomal storage diseases. Lysosomes are membrane-bound compartments found in the cells of the body. These compartments contain enzymes, which are responsible for the breakdown of many large molecules. These molecules are continuously made and broken down in our bodies and this process is necessary for appropriate mental and physical development. Each enzyme in the lysosome is responsible for a certain step in the breakdown of the molecule. Many lysosomal storage diseases are caused by the absence of one specific enzyme that leads to the build-up of molecules in the lysosome. However, in I-Cell disease, many lysosome enzymes are missing. This is because the enzymes are lacking a signal that is necessary for them to get inside the lysosome. Instead of getting into the lysosome and breaking down the molecules found there, the enzymes are found outside the lysosome. This leads to the build-up of molecules inside the lysosome. You may hear this disorder called a “targeting” defect. This refers to the fact that the enzymes lack the signal that targets them to the lysosome in the cell; thus they end up in a place where they are unable to do their work.

Not every enzyme within the lysosome is missing, however. It has been shown that some enzymes are able to enter through a different pathway that doesn’t require the signal on the enzymes.

I-Cell disease is closely related to Pseudo-Hurler Polydystrophy (Mucolipidosis III). Both disorders are “targeting “ defects. Pseudo-Hurler Polydystrophy disease present with much less severe clinical findings. The enzyme that is responsible for putting the targeting signal on the lysosome enzymes that is not working in both I-Cell disease and Pseudo-Hurler Polydystrophy is N-acetylglucosamine-1-phototransferase.

The build up of molecules that is caused by the targeting defect is gradual and interferes with the correct function of the cell. It eventually leads to the clinical features of ML II. Features may progress over time.

What are the clinical features of I-Cell Disease (ML II)?

Individuals with ML II typically have severe psychomotor retardation. Typically, failure to thrive and developmental delay are obvious by the age of 6 months. The degree of mental retardation is variable but is usually severe and progressive. Individuals with ML II have the coarse facial findings that can be characteristic of some lysosomal storage diseases and include a high forehead, puffy eyelids, flat nasal bridge, macroglossia (large tongue) and coarsening of facial features. Radiologically, they have dysostosis multiplex (abnormal bone formation in multiple bones of the body). Skeletal problems are typically severe and include kyphoscoliosis (curvature of the spine), vertebral body anomalies and claw-hand deformities. Individuals with ML II are prone to carpal tunnel syndrome and can experience pain and loss of feeling in their fingertips. Other musculoskeletal problems include hernias and joint contractures and restriction.

From a cardiovascular standpoint, individuals with ML II may have cardiomegaly / cardiomyopathy (thickening and weakening of heart muscles). Other organs may be enlarged as well, including the liver (hepatomegaly) and to a lesser extent, the spleen (splenomegaly). Other medical concerns include recurrent upper respiratory, ear infections and corneal clouding.

A specific dental problem associated with ML II is gingival hyperplasia (prominent gums) as well as late and poorly formed teeth.

Unfortunately, due to the severity of progression of I-Cell disease, individuals with this disorder typically do not live past the 1st decade. Many pass away within the first 3-4 years of life.

How is I-Cell disease (ML II) inherited?

ML II is not contagious and cannot be “caught.” It is a genetic condition, which means that it is caused by a change in the instruction that direct the way our bodies grow and develop. These instructions are called genes. People typically have two copies of all their genes, including the gene for ML II (N-acetylglucosamine-1-phototransferase). One copy is inherited from the mother in the egg, and one from the father in the sperm.

Only when there is a change in the gene code is there a possibility that the disease will occur. For a person to have ML II, they must inherit changes in both of their genes resulting in instructions that do not function properly. This is known as autosomal recessive inheritance.

For a couple to have a child with ML II, both parent must have at least one changed copy of the gene which they pass on to their child. Parents do not have control over which genes they pass on to their children.

If a person has one changed copy of the gene and one normal copy of the gene they are said to be a “carrier” of the condition and will not show any symptoms of ML II. If two parents are both carriers, they have a 1 in 4 (25%) chance of having a child with ML II in each pregnancy.

What testing is available to determine if my child has I-Cell disease (ML II)?

Testing for lysosomal storage diseases is typically performed in conjunction with a genetics evaluation. A genetics team takes into account the medical history and clinical features of a patient to determine what type of genetic testing is appropriate. For the diagnosis of ML II, a blood test should show increased activity of lysosomal enzymes in the serum. A urine spot screen that screens for other lysosomal storage disease such as oligosaccharide and muccopolysaccharide disorders may not be as helpful in detecting mucolipidosis disorders. Another test that can be performed is to have a skin biopsy and measure activity of N-acetylglucosamine-1-phototransferase. The skin sample should show decreased activity of this enzyme.

For families who have had a child diagnosed with ML II, prenatal diagnosis is available in future pregnancies by looking at enzyme activity through Chorionic Villus Sampling (CVS) or amniocentesis.

What type of treatment is available for I-Cell Disease (ML II)?

Individuals with ML II should have routine follow-up with Genetics, Orthopedics, Cardiology, Ophthalmology, Pulmonary, Physical Therapy, and ENT as needed. Dentistry follow-up is also very important. Currently, there is no cure to stop the progression of symptoms of ML II and treatment is aimed at addressing the individual problems as they arise.

For some lysosomal storage diseases, bone marrow transplant has been trialed as an experimental therapy, but there are no conclusive results on the long-term benefits. Additionally, some trials have been performed with Pamidronate, a drug that helps to increase bone strength. Ask your specialist for more information on these options.

[ top ]