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THE FAS GENE

We have found genetic changes or mutations that seem to be factors in the development of ALPS. In over 83% of the ALPS patients, we have found an alteration in a gene that encodes a cell component, or protein, called Fas. This alteration causes the gene to produce abnormal Fas protein. We do not completely understand how abnormal Fas protein leads to ALPS, but it clearly does. We still need to identify other genetic and non-genetic factors that contribute to the development of ALPS.

The Fas protein is one of several proteins that are important for apoptosis, the normal process through which cells die. Fas controls the life span of certain cells, particularly the lymphocytes. Like people, cells have a normal life span in which they grow, do their job, and then die. The mutated Fas protein does not work well, and can't give the cells the message that it is time to die. Although most ALPS patients have one normal and one altered copy of the Fas gene, the altered protein is able to interfere with the function of the normal one.

However, Fas mutations do not explain all cases of ALPS. About 17% of people with ALPS do not have a Fas mutation. In some of them there are alterations in other proteins known as Fas-ligand and Caspase-10. In some ALPS patients a genetic alteration has not yet been found. Also, there are many relatives of ALPS patients who have a Fas mutation and do not have ALPS. We believe that other genes and environmental factors also play a role determining which people get ALPS.

ARE MY CHILDREN AT RISK IF I HAVE A FAS GENE MUTATION?

There are many people who have no signs of ALPS, yet have a Fas mutation. Individuals with a Fas mutation have a 50/50 chance of passing the Fas mutation on to their children. That means that each child has a 50% chance of inheriting the unaffected gene and a 50% chance of inheriting the altered gene. This chance is the same for each child. In other words, if you have 5 children and they have each inherited the Fas mutation, the sixth child still has the same 50/50 risk of inheriting the Fas mutation. Of the children who inherit the Fas mutation, approximately half of them will develop some features of ALPS. This figure is based on the 98 people we have studied so far at NIH who have a Fas gene mutation. Of these 98 people with the Fas gene mutation, 48 have enough symptoms to be diagnosed with ALPS and additional persons have some features of ALPS. Children who have inherited the unaltered Fas gene have almost no chance of developing ALPS.

HOW TO EXPLAIN ALPS TO YOUR KIDS

It may seem easier not to tell your children anything about ALPS, but children, like adults, often want to know "why?" and don't like to be left in the dark. The more children understand about ALPS, the fewer fears and misunderstandings they may have. The following is one way we have explained ALPS to a child. You may find these ideas helpful for your family.

ALPS IS A PROBLEM WITH THE IMMUNE SYSTEM.

Usually, the immune system attacks germs, as an army would attack its enemy. The soldiers are called lymphocytes. They go around the blood stream and find germs. After the soldiers kill the germs, their job is done and it is time for them to go away and die. In ALPS, the soldiers donít hear the message to die. They stay and hang out in places like your spleen and the lymph nodes found under your cheeks, making them really big. Sometimes, the soldiers become confused and they attack members of their own side, such as the red blood cells and platelets in your body. Without enough red blood cells, you may feel tired. Without enough platelets, you may get nosebleeds, red spots on your skin and bruises. Sometimes you may need to take medicine or get a transfusion of new blood. Sometimes you have to be extra careful not to bump your belly because your spleen is fragile. Even though living with ALPS can be hard, all kids still go to school, and most adults work. All have responsibilities, contribute to their communities in many ways, have friends, and have fun.