A type of mucolipidosis that is caused by a deficiency in UDP-N-acetylglucoseamine-1-phosphotransferase resulting in the accumulation of mucopolysaccharides and mucolipids in tissues, such as nerve, liver, and muscle tissues
Mucolipidosis is a lysosomal storage disease caused by a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase. The enzyme is involved in the phosphorylation of carbohydrate residues on N-linked glycoproteins. Without N-acetylglucosamine-1-phosphotransferase or the inadequate levels of this enzyme, mucopolysaccharides and mucolipids tend to accumulate inside the cell. There are different types of mucolipidosis and one of them is called the inclusion-cell disease (also referred to as mucolipidosis type II).
The inclusion-cell disease (I-cell disease) is inherited in autosomal recessive manner. This means that the individual with this disease bears two copies of the defective gene, e.g. GNPTA or GNPTAB. This gene is located on the long arm of chromosome 4. Normally, the gene codes for the enzyme UDP-N-acetylglucoseamine-1-phosphotransferase. The enzyme, in turn, catalyzes the N-linked glycosylation of asparagine residues with mannose-6-phosphate (i.e. a lysosome recognition marker). Pathological mutation in GNPTA gene or GNPTAB gene could lead to a deficiency or a dysfunctional enzyme, and therefore, the failure of properly tagging mannose-6-phosphate to its protein structure. Thus, instead of proceeding to the lysosome, the enzyme is secreted extracellularly.
Individuals with I-cell disease have symptoms such as coarse facial features, skeletal deformities, hepatosplenomegaly, short-trunk dwarfism, and mental retardation. Microscopic examination of their fibroblasts reveals intracytoplasmic inclusions (thus, the name). These inclusion bodies are actually the accumulated mass of carbohydrates, lipids, and proteins.
- I-cell disease