I-cell disease

The I- cell disease, also referred to as mucolipidosis II, is a very rare autosomal recessive lysosomal storage disease.

Discovery

Leroy and DeMars described first time in 1967, the I - cell disease, which is similar to mucopolysaccharidosis type I ( Hurler syndrome ). However, the patients showed no mucopolysaccharide excretion. For this, the two researchers were able to inclusion in the fibroblasts of the skin (English: inclusin -cells ) detected. The inclusions gave the disease its English name I -Cell Disease.

The disease is extremely rare. The incidence of both Mukolipidosen II and III together is about 0.3: 100,000.

Cause

The cause of the disease is a lack of activity of the enzyme N- acetylglucosaminyl -1 - phosphotransferase ( EC 2.7.8.17 ), which causes a large portion of lysosomal enzymes can not enter the inside of the lysosomes. The targeting of lysosomal enzymes is disturbed by a defect in the phosphotransferase that normally allows the synthesis of a specific sorting signal. Labeling with mannose -6-phosphate can not occur, and the lysosomal enzymes can not be sorted. You can reach downstream of the plasma membrane into the extracellular matrix.

Symptoms

The symptoms of the disease are usually already at birth, no later than a few months after birth visible. The symptoms are similar to those of Hurler syndrome ( mucopolysaccharidosis I), but are used to observe usually. In addition, the patients do not show mucopolysaccharide exudates. The symptoms show from family to family and even within a family, a large variety of options.

After Kornfeld and Sly following clinical features are possible:

1 skeleton Kyphoscoliosis, dislocation, clubfeet, joint contractures, vertebral deformities, short stature, dysostosis multiplex

2 Internal Organs Hepatosplenomegaly, cardiomegaly, heart defects

3 face and head Coarse facial features, exophthalmos, hyperplastic gums, scaphocephaly, held open mouth, deep sunken nose

4 eyes Corneal opacities, swollen eyelids

5 skin Thickness rough skin

6 CNS Severe psychomotor and mental retardation

Diagnosis

By biochemical determination of the activity of lysosomal enzymes in the serum, the diagnosis can be made. The ratio of intra-and extracellular activity of lysosomal enzymes and the activity of the phosphotransferase in cultured fibroblasts, are other possible laboratory parameters.

The inclusions in the fibroblasts are accumulations of mucopolysaccharides, lipids, and oligosaccharides.

Genetics

The enzyme N -acetylglucosamine -1 - phosphotransferase consists of three subunits ( alpha, beta and gamma), which are encoded by two different genes. A gene encoding this case the α - and β -, the other gene, the γ - subunit. In autosomal recessive inherited disease, the I- cell GNPTA gene ( GNPTAB ) is mutated for the α and β subunit gene locus on chromosome 12 q23.3. The gene for the γ - subunit ( GNPTG ), however, is on chromosome 16 p13.3 gene locus and not affected by the mutation.

Therapy

A cure is so far excluded. The treatment is purely symptomatic.

Forecast

The prognosis is very unfavorable. Sufferers usually do not survive the first decade of life. Cause of death are usually recurrent pneumonia.