Autoimmune Lymphoproliferative Syndrome (ALPS) : Treatments, The Fas Gene

by National Institute of Health

(Page 3 of 4)

Treatments

Blood Transfusions are useful to replace red blood cells when anemia is severe.

Vaccines are important to help prevent infections. The fewer infections you have, the less often you will need to "call in the troops." In addition to all the childhood vaccinations, it is important to get a yearly flu shot and boosters as needed. People with allergies to eggs should discuss this with their doctor prior to receiving a flu shot. Gene Therapy is unfortunately not likely to work for ALPS.

Does ALPS Run In Families?

Children can inherit ALPS from one of their parents. The process of apoptosis is controlled by several genes. Most people with ALPS have an altered gene that plays a major role in apoptosis. The altered gene may be passed from one generation to the next. Before discussing what this gene does, we need to describe some basic information about genes and how they work.

A Brief Introduction to Genetics

Genes, which are made of DNA, are located on chromosomes in the cells of our body. We have two copies of each gene, except for the genes on the sex chromosomes. Genes act as the blueprint for the development and operation of our bodies. Each gene contains the instructions for making one of the building blocks of a cell. We each have around 100,000 genes that determine who we are, what we look like, and how our bodies work. By chance, every person has approximately 10-12 genes that don't work as well as they should or don't work at all. These genes are mutated. That is, the DNA is slightly different in mutated genes. Not all changes, or mutations, are harmful. Sometimes these changes cause no problems at all, but sometimes they cause human disease. Sometimes it takes alterations in several genes to cause problems. Other times the genetic mutation interacts with the environment to cause health problems.

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 don't 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.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.