What causes MPS I?

MPS I is a genetic disorder. When most people think of genetic disease, they think of a health problem that gets passed down from father or mother to child and so on. While many genetic diseases are passed down through the generations in an obvious way, some genetic diseases are “hidden,” or recessive, and only show up when both genes in an individual are affected. MPS I is one such disease.

Most families with a child with MPS I do not have a family history of this genetic disorder. To understand this better, it is important to understand some basics of genetics. All humans are formed with two complete sets of genes, one set from each parent. So any individual has half his genes from his mother and half from his father. Together, the individual has 100% of the genes required to live.

For each enzyme made in the body, there are two copies of the same gene to produce it, one from the mother and one from the father. If one gene happens to be defective, then the body may only produce 50% or less of the normal level of enzyme associated with that gene. The body is quite resilient, and even the 50% level of enzyme can be more than enough to keep the person healthy. However, if the copies from both the mother and the father are not functioning correctly, the individual will produce little or no enzyme and will have symptoms of the disease.

As mentioned earlier, MPS I is a recessive disorder. This means it occurs only if both copies of the alpha-L-iduronidase enzyme gene inherited by the individual are defective. This happens when each parent is a “carrier” of the defective gene, i.e., each parent has one normal version of the gene that can produce the necessary enzyme but also “carries” one defective version of the gene that cannot produce it properly.

The figure below shows how the MPS I gene may be passed from one generation to the next.


Fig.1) Inheritance Pattern of MPS I.

As the figure above describes, any child born of carrier parents has a three out of four (or 75%) chance of having at least one normal gene, and therefore no disease, and a one out of four (or 25%) chance of inheriting a copy of the defective gene from both parents and thus being affected with the disorder. There is also a two out of three (or 66%) chance that an unaffected offspring will still be a carrier of the defective gene that causes MPS I.

Family screening

Because MPS I is an inherited disorder, family screening is extremely important. When a diagnosis for an individual is made, it is important to find out whether other siblings may also be affected. A genetic counselor can be a valuable resource to help you understand how MPS I is inherited in families, and to help determine if others in the family will want to consider genetic testing for MPS I as well.