Mucopolysaccharidosis I (MPS I) is a rare genetic disorder that affects many body systems and that leads to organ damage. It is caused by an alteration in the gene that makes an enzyme called alpha-L-iduronidase. Because of this alteration, cells either produce the enzyme in low amounts or cannot produce it at all. The enzyme is needed to break down substances called “glycosaminoglycans” (GAGs) which are by-products of chemical reactions in the body’s cells. If GAGs are not broken down, they build up in the cell, eventually leading to cell, tissue, and organ damage.
GAGs, previously called mucopolysaccharides, are long chains of complex sugar molecules which are located primarily on the outside surface of cells. The body uses them in the building of bones, cartilage, skin, tendons and many other tissues in the body. GAGs form part of the structure of the body and also give the body some of the special features that make it work. For example, the slippery, gooey joint fluid that lubricates your joints contains mucopolysaccharides. The rubbery resilient cartilage in your joints is another example. All tissues have some of this substance as a normal part of their structure. However, individuals with MPS I have too much GAG in their body.
To understand how GAG accumulates and causes MPS I, it is important to understand that in the course of normal life, there is a continuous process of building new GAGs and breaking down old ones – a recycling process. This ongoing process is required to keep your body healthy. The breakdown and recycling process requires a series of special biochemical tools called enzymes.
To break down GAGs, a series of enzymes works in sequence one after another. The GAG chain is broken down by removing one sugar molecule at a time, starting at one end of the GAG chain. Each enzyme in the process has its special purpose in the body and does one very specific action, just like a screwdriver works on screws and a hammer works on nails.
As mentioned earlier, people with MPS I are missing one specific enzyme called alpha-L-iduronidase, which is essential in the breakdown of certain GAGs called dermatan sulfate and heparan sulfate. The incompletely broken down dermatan sulfate and heparan sulfate remain stored inside cells in the body and begin to build up, which interferes with the normal functioning of cells and can cause progressive damage. Some individuals with MPS I may initially show few signs of the disorder, but as more and more GAGs accumulate, symptoms start to appear.
In MPS I, glycosaminoglycan (GAG)-engorged cells accumulate and displace healthy normal cells in tissue and organs such as the liver and spleen, causing a host of signs, including skeletal deformities, coarse facial features, and an enlarged liver and spleen.