The following points highlight the seven major diseases caused due to abnormalities in the synthesis of glycoproteins.
1. Many cancer cells exhibit different profiles of oligosaccharide chains on their surfaces and some of which contribute to metastasis.
2. Carbohydrate-deficient glycoprotein syndrome (CDGS) is caused due to defects in the biosynthesis of N-glycan chains (e.g., due to deficiency of Glc NAC transferase (II) particularly affecting the central nervous system.
3. Paroxysmal nocturnal hemoglobinuria is an acquired mild anemia characterized by the presence of the hemoglobin in urine due to hemolysis of red cells, particularly during sleep. This disease is caused by the acquired defect in the biosynthesis of lucophosphatidylinositol (GPI) structures of decay accelerating factor (DAF) and another protein CD59.
4. I-cell disease is an uncommon condition characterized by severe progressive psychomotor retardation and a variety of physical signs with death even occurring in the first decade. The patients suffering from this disease lack almost all of the normal lysosomal enzymes.
These enzymes ultimately lack Man 6-P and are secreted from cells (e.g., into the plasma) rather than targeted to lysosomes. These lysosomes are thus deficient in certain hydrolases, do not function properly and accumulate partly digested cellular material manifesting as inclusion bodies.
5. Pseudo-Hurler polydystrophy is another genetic disease closely related to I-cell disease. It is a milder condition and patients may survive to adulthood. In this disease, the Glc NAC phosphotransferase interacts with lysosomal enzymes and the retention of some catalytic activity results in a milder condition.
6. The degraded glycoproteins can lead to various diseases. The best recognized of these diseases are mannosidosis, fucosidosis, sialidosis, aspartylglycosaminuria, and Schindler’s disease due to respectively deficiencies of α-mannosidase, α- fucosidase, a-neuraminidase, aspartylglu-cosaminidase, and N-acetylgalactosa-minidase.
These diseases usually exhibit mental retardation or other neurologic abnormalities. Vacuolization of cells are also observed in some disorders. The abnormal degradation products e.g., oligosaccharides that accumulate due to enzyme deficiency are present in urine in these diseases. No confirmative treatment has yet been established for these diseases.
7. Glycoproteins have also direct or indirect roles in a number of other diseases such as
(i) The influenza virus has a neuraminidase that eludes the newly synthesized progeny from infected cells.
(ii) HIV-l, the causative agent of AIDS, attaches to cells via one of its surface glycoproteins, gp 120.
(iii) Rheumatoid arthritis is associated with an alteration in the glycosylation of circulating immunoglobulin-y (IgG) molecules, such that they lack galactose in their Fc regions and terminate in Glc NAC.
Mannose-binding protein, a C-lectin synthesized by liver cells and secreted into the circulation, binds mannose, Glc NAC, and certain other sugars. It can thus bind the galactosyl IgG molecules contributing to chronic inflammation in the synovial membranes of joints.
This protein can also bind the above mentioned sugars when they are present on the surfaces of certain bacteria, fungi, and viruses preparing the pathogens for destruction by the complement system. Deficiency of this protein in young infants, due to mutation, renders them very susceptible to recurrent infections.
The effective treatments for diseases in which these molecules are involved fully depend on the studies of glycoproteins and other glycoconjugates.