Sometimes operations at the cell level can go wrong, resulting in changes to the normal chemical patterns in DNA. This change to DNA is called a mutation, and it can affect the way the genes containing that DNA operate. Mutations are not necessarily bad--every human has an estimated eight to ten genes that are mutated, and most of these have little or no impact on the body.

However, if a gene that controls a vital cell function--like the production of enzymes required for waste breakdown--is mutated, problems can occur, including certain diseases. This is the case with lysosomal storage disorders (LSDs): people with these diseases have mutated forms of the genes responsible for producing enzymes that break down certain waste products. The mutated gene doesn't operate properly, so the enzymes malfunction or aren't produced in sufficient amounts. Thus the waste products don't get broken down and instead are stored in cells' lysosomes, causing a variety of symptoms.

If a gene mutation arises within a single cell in the body, it will likely have little effect because the majority of the body's cells will still have the normal gene. Even as cells continue to replicate themselves, most of the replications will come from normal cells, so the number of cells with the mutation will remain negligible.

However, if a mutation occurs in a sperm or egg cell, the mutated gene will get passed onto offspring during sexual reproduction. Since the offspring's very first cell carries the mutated gene, every subsequent cell replicated from it will also have the mutation. Whether the affected gene causes a genetic disease depends on whether it is dominant or recessive as well as on the condition of the other gene in its pair.

Most of the LSDs are autosomal recessive disorders; the two exceptions, Fabry and MPS II, are X-linked recessive. The autosomal disorders are caused by a mutated gene on one of the autosomal chromosomes, while with Fabry and MPS II the gene mutation is on the X chromosome.

The “recessive” part means that the mutuated gene’s faulty operation can be “overridden” by the presence of an unaffected gene in the other half of the pair. Thus if a person inherits an LSD-associated gene from only one parent, the other unaffected gene may still allow enough enzyme production for the person to remain without symptoms. These people are called carriers, and can still pass the mutation on to their children. If a person inherits an LSD-associated gene from BOTH parents, however, he or she will develop the LSD.

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