I Cell Disease Dictionary Definitions

I cell disease is a lyosomal mucolipidosis. The storage disease is caused by a mutation of the GNPTA gene with the gene locus q23.3 on chromosome 12. The symptomatic treatment is mainly through the administration of bisphosphonates.

What is I cell disease?

According to abbreviationfinder, a biochemical determination of the lysosomal enzyme activity in the serum can confirm the diagnosis. This determination gives an erroneous ratio of intra- and extracellular activity.

Storage diseases are characterized by the accumulation of various substances in cells and organs of the human body. It is a heterogeneous group of diseases that can be divided into several sub-forms. In addition to glycogenoses, mucopolysaccharidoses and lipidoses, medicine differentiates between sphingolipidoses, hemosideroses and amyloidoses depending on the deposited substance.

Lysosomal storage diseases affect the lysosomes. These are tiny, membrane-coated cell organelles in eukaryotes. Lysosomes are formed by the Golgi apparatus and are equipped with hydrolytic enzymes and phosphatases. With the help of their enzymes, they should primarily digest foreign substances and endogenous substances.

The I cell disease is a lyosomal mucolipidosis with two different subtypes. Leroy and DeMars first documented the disease in the 1960s and pointed to the similarity to mucopolysaccharidosis type I, known as Hurler’s disease. The name of the disease goes back to the fibroblast inclusions, the so-called inclusin cells in the skin of the patient.


I-cell disease is caused by a lack of activity of N-acetylglucosaminyl-1-phosphotransferase. The limited activity of this enzyme prevents a large part of the lysosomal enzymes from reaching the interior of the lysosome. The regulation of the lysosomal enzymes is characterized by the activity of the phosphotransferase.

It enables the synthesis of a sorting signal in a healthy organism. This process is disrupted in I cell disease. Therefore, no labeling with mannose-6-phosphate takes place. For this reason, the lysosomal enzymes are no longer sufficiently sorted and migrate uncontrolled via the plasma membrane into the extracellular matrix.

This is caused by a mutation in the GNPTAB gene. It deprives N-acetylglucosaminyl-1-phosphotransferase of its functionality and thus its ability to catalyze mannose-6-phosphate synthesis. The transport of lysomal enzymes is thus disrupted. The N-acetyl-glucosamine-1-phosphotransferase consists of the subunits alpha, beta and gamma. They are encoded on two genes.

The hereditary I-cell disease affects the GNPTA gene on chromosome 12. There is a mutation in gene locus q23.3. An incidence of around 0.3 in 100,000 is given for the rare disease. Inheritance is autosomal recessive. In order for the disease to be passed on, both parents must carry the defective gene.

Symptoms, Ailments & Signs

In most cases, the symptoms of I-cell disease can be observed immediately after birth or a few months later at the latest, and their characteristics are similar to those of Hurler syndrome. Unlike Hurler syndrome patients, those with I cell disease do not exhibit mucopolysaccharide secretion.

The individual symptoms of the disease are subject to a large variety of variations. Kornfeld and Sly summarize clinical features of the skeleton, internal organs, eyes, skin, central nervous system, and face. The skeleton is so commonly affected by kyphoscoliosis and hip dislocations.

Clubfoot, joint contractures, and vertebral deformities may also be present. The same applies to short stature and dysostosis multiplex. The disease can manifest itself in the internal organs in the form of hepatosplenomegaly and cardiomegaly or heart defects. The patient’s face shows coarse facial features.

Exophthalmos, hyperplastic gums or scaphocephaly are also typical symptoms. Equally characteristic are an open mouth and a deeply sunken bridge of the nose. The eyes of those affected often show clouded corneas or swollen eyelids. The skin is thick and rough, with severe central nervous system psychomotor or mental retardation.

Diagnosis & course of disease

The first suspected diagnosis of the I-cell disease can be made based on the medical history. A biochemical determination of the lysosomal enzyme activity in the serum can confirm the diagnosis. This determination gives an erroneous ratio of intra- and extracellular activity.

The activity of the phosphotransferase in the fibroblasts can also be determined to confirm the diagnosis. The inclusions correspond to either mucopolysaccharides, lipids or oligosaccharides. Molecular genetic diagnostics can dispel any remaining doubts. With a corresponding history, the disease can also be diagnosed in the context of prenatal diagnostics.

Because of the low prevalence, however, prenatal testing is actually only recommended if there is a family history. The course of the disease depends on the symptoms in the individual case and is not directly predictable. However, most patients hardly survive past the age of ten. However, milder forms in individual cases cannot be completely ruled out.


I cell disease can lead to various complications and symptoms. However, these are only recognized late, so that the I-cell disease can only be diagnosed late. The symptoms are relatively inconsistent, which often makes treatment difficult. This usually leads to complaints and malformations on the skin, the eyes and also on the internal organs.

In the worst case, the person affected can go blind or die directly from organ failure. Furthermore, there is a pronounced short stature and also to heart problems. The eyelids are often swollen and there is reduced intelligence and mental retardation. It is not uncommon for those affected to be dependent on the help of other people in everyday life due to the retardation in order to be able to master it.

The quality of life of the patient is greatly reduced by the I-cell disease. As a rule, there are no special complications in the treatment of the disease. Drugs and psychological treatments are used to relieve symptoms. However, a complete and causal treatment of this disease is not possible. Life expectancy is reduced by the disease.

When should you go to the doctor?

The I-cell disease is usually diagnosed immediately after the birth of the child. Whether further treatment measures are necessary depends on the type and severity of the symptoms. Slight malformations do not necessarily have to be treated. Clubfeet and deformities of the vertebrae, on the other hand, are serious malformations that must be treated surgically and with medication. Parents should consult a specialist immediately if the doctor in charge at the maternity hospital has not already done so.

If the symptoms result in an accident or a fall, the child must be taken to the hospital or the parents should call the emergency services immediately. In the case of severe malformations, which may also affect the child’s psyche later in life, a therapist should be consulted in addition to medical treatment. The I-cell disease therefore requires a medical clarification in any case. The right contact person is the pediatrician or a specialist in hereditary diseases. In the event of visual disturbances, an ophthalmologist should also be consulted.

Treatment & Therapy

I cell disease is considered incurable. A causal therapy therefore does not exist. Treatment is exclusively symptomatic and supportive. The psychotherapeutic care of affected families makes up a large part of supportive therapy. The symptomatic therapy depends on the individual case. The bone symptoms are often treated with the administration of bisphosphonates.

These drugs are known from the treatment of osteoporosis and have a high affinity for the bone surface. They bind to the bone, especially in the region of the resorption lacunae. They inhibit the bone-degrading osteoclasts and in this way reduce bone resorption. The drugs belong to the pyrophosphate analogues with a carbon-containing POP bond.

An enzymatic hydrolysis does not take place on them. The most recent of these substances are the aminobisphosphonates. Alendronate, clodronate, etidronate, ibandronate, pamidronate and risendronate are also approved in Germany from the same drug group. The same applies to tiludronate and zoledronate.

In addition to these drugs, bone marrow transplantation is also an option for treating I-cell disease. However, the success of this treatment has been limited in previous cases. Gene therapies are now being investigated as a new therapeutic approach for gene defects. Gene therapies have shown initial success in animal models. So far, they have not been able to be used in practice on humans. However, this relationship will probably change in the future.

Outlook & Forecast

The I-cell disease is an inherited disease that cannot be treated symptomatically to date. The prognosis is correspondingly negative. Although the symptoms can be significantly reduced by early therapy, the I-cell disease almost always takes a serious course.

Short stature and damage to internal organs and the head are already reducing life expectancy considerably. Furthermore, malformations in the area of ​​the face, skin and eyes can lead to a reduction in life expectancy, but primarily also in the quality of life of those affected. Some of those affected reach the age of 40 or 50, but most of the sufferers die in childhood or adolescence.

If the I-cell disease is not treated, the sufferers often die in the first few years of life. The prognosis is therefore rather negative. Nevertheless, the prospect of a relatively symptom-free life is given if the patient is treated as part of a comprehensive therapy and, if necessary, is accommodated in a facility for physically disabled people. Physiotherapy and therapeutic measures can significantly improve the well-being of the patient in the long term.


I-cell disease can only be prevented by molecular genetic testing prior to family planning. As part of the prenatal diagnosis, expectant parents can also decide to have an abortion.


In most cases, those affected by I-cell disease have no or very few follow-up measures available. The disease must be detected by a doctor as early as possible so that further deterioration of the symptoms can be prevented. Since this is a genetic disease, a genetic examination and counseling should always be carried out first if you wish to have children, in order to prevent the I-cell disease from being passed on to descendants.

Most patients with this disease are dependent on taking various medications. It is important to ensure that the dosage is correct and that the medication is taken regularly. If anything is unclear, side effects or questions, always consult a doctor first.

Likewise, many of those affected need psychological support with this disease, whereby loving conversations with parents or with relatives can also have a positive effect on the course of the disease. Those affected need help and support in everyday life from their own family. In many cases, the I-cell disease significantly limits or reduces the life expectancy of the person affected.

You can do that yourself

Patients suffering from I-cell disease can resort to various conservative and alternative treatment methods. Conservative therapy focuses on relieving symptoms and discomfort.

The use of aids such as crutches or orthopedic insoles can slow down the progression of the respective deformities and thus reduce the pain. Medications help to relieve pain and can be supplemented with alternative measures such as massage or acupuncture. However, alternative therapies should be discussed with the responsible doctor beforehand. The doctor may be able to refer the patient directly to a homeopath or give further tips on how to treat the symptom in question.

Since the I-cell disease is usually fatal despite all treatment options, therapeutic advice should be sought. Not only the person concerned should deal with his fears. Relatives and friends usually also need support in dealing with the disease and a possibly negative course. Participation in a self-help group is also an option for the patient and their relatives. Contact with other affected people helps to accept the disease, and often other sufferers can also name further treatment measures and strategies for everyday life with the I-cell disease.

I Cell Disease