Purpose of this Page

First, the purpose of this page is to provide a starting point for parents of children who have recently been diagnosed with Fanconi Anemia. Consider this a starting point for learning more about Fanconi Anemia--with links to sites with much more information. If you came across this page first, I hope I can guide you to the best sites to gain the the quickest understanding of Fanconi Anemia.

Secondly, this site aims to provide detailed genetic information about Fanconi Anemia--information that you can't find on any other site. You may find this information useful in assessing your future reproductive options, especially if you are considering Preimplantation Genetic Diagnosis (PGD). The parents of the newly diagnosed may only see this information as a curiosity--but bookmark this page, you may find it useful later.

What is Fanconi Anemia?

Fanconi Anemia is a very rare, inherited genetic disease that causes severe, life-threatening aplastic anemia--which means a deficiency of all types of blood cells. Ultimately, the patients experience bone marrow failure. A lack of immune cells will lead to infections that the patient cannot successfull combat, the lack of red blood cells will cause fatigue, and low platelet counts will cause sponaneous bleeding. Blood counts are normal at birth, but aplastic anemia develops insidiously and presents in most cases between 5 and 10 years of age; however, in some cases, it presents in adolescence or even in adult life.

FA patients may also hae a variety of noticeable birth defects, ranging from the minor to serious. These defects may affect every major system in the body. The most common defects are thumb abnormalities (missing thumb, small thumb, crooked thumb, etc.), dark skin spots called "cafe' au lait" spots, and short stature.

FA patients experience a high incidence of leukemia (18-20%), usually of the acute myeloid type. FA patients also have a higher incidence of cancer than the general population.

The estimated incidence of FA is approximately 1 case in 360,000 live births. The results in a carrier frequency of 1 per 300 individuals.

For the Newly Diagnosed

If you've come across my page as your first Internet search for Fanconi Anemia, I would recommend you take a look at these other sites immediately:

Fanconi Anemia Research Fund (FARF), Inc - the research fund that has funded much of the research that has lead to a dramatic increase in the understanding of the causes of Fanconi Anemia and improved treatment options. They also publish the Fanconi Anemia - A Handbook for Families and Their Physicians and Fanconi Anemia - Standards for Clinical Care. These are available online--I recommend you start reading them immediately. Also, you can contact FARF and they'll be glad to mail you nicely printed, bound, volumes of both texts.

If you are not in the United States, check this page for a Fanconi Anemia interest group in your country.

For information on connecting with other families affected by FA, see this page.

Diagnosis of Fanconi Anemia

The initial suspicion of Fanconi Anemia is usually through either 1) the existence of birth defects typical of FA, 2) the development of aplastic anemia (or bone marrow failure), 3) the development of myelodysplasia (abnormal production, maturation, and appearance of blood cells) or leukemia.

No matter why FA was initially suspected, the definitive test for FA is a chromosome breakage test. There are two tests currently used for this--the diepoxybutane (DEB) test, and the mitomycin C (MMC) test. In both tests, a small sample of blood is taken from the patient. Then, the blood's lymphocytes (a type of white cell) are exposed to a chemical agent (either DEB or MMC). These chemical agents cause the chromosomes in FA cells to break and rearrange; the chromosomes of normal cells are more stable. The amount of breakage is quantified and compared to a standard scale for normal cells and FA cells--if the results are in the range of the FA cells, it is concluded the patient has FA.

If the specific disease causing mutation is know for a family, that can be tested for directly.

This is an overview of the diagnosis of FA; see the Handbook for Families and Their Physicians (prior section) for a more detailed explanation. It's also worth a visit to the Arleen D. Auerbach lab website. You may have had your diagnostic testing performed by her lab.

Available Treatment Options

Drug Therapy: Between 50-75% of FA patients respond to a group of drugs known as androgens, such as oxymetholone. These are artificial male hormones that often stimulate production of one or more types of blood cells for extended periods of time. They are most effective for red blood cells, but often increase platelet production as well. Another class of drugs, hematopoietic growth factors (GM-CSF, G-CSF, erythropoietin) has also recently been used for FA patients with promising results; these factors occur naturally in the body--adding more further stimulates production of blood cells.

Transfusions: A supportive form of care is to transfuse donated blood cells into the FA patient. If the patient is lacking platelets, then only platelets are transferred; if red blood cells are needed, only those as transferred. This helps to temporarily restore blood counts to more normal levels. However, extensive transfusions can complicate a bone marrow transplant. So it's best to use it only for a short time, use irradiated blood products only, and have dedicated donors providing the donated blood. Some patients have had extensive tranfusions, however, numbering in the hundreds.

Bone Marrow Transplant (BMT): This is currently the best hope for FA patients. A successful transplant cures the aplastic anemia aspect of FA, which is the most life threatening. It does not cure FA--the patient still has a higher risk of solid tumors, as the defect in chromosome repair is present in every cell in the patients body (except the marrow from the transplant, of course). The best success for BMTs comes from matched sibling donors--a brother or sister that has an exact HLA (human leukocyte antigen) match with the patient. The odds are 1 in 4 that a sibling will be a perfect match. Since 1994, he two year survival rate for sibling matches has been 80%--and it is improving all the time. Don't have a matched sibing? See the section on Preimplantation Genetic Diagnosis (PGD) on my following pages. It's also possible to do a stem cell transplant from the umbilical cord blood of an HLA-matched brother or sister (again, see PGD, below). If an HLA-matched relative is not available, then it is possible to do a transplant with an unrelated donor--either perfectly matched or partially matched. The success rate with unrelated donors is not as good as that of related donors--but it is getting better all the time.

In the United States, there are two doctors well known for their BMT programs for FA patients. Dr. Richard Harris, MD is at the Children's Hospital Medical Center in Cincinnati, Ohio. Dr. John Wagner, MD, is at the University of Minnesota School of Medicine, Minneapolis, Minnesota. Both doctors and transplant centers have excellent reputations for BMT procedures for FA patients. FA families, it appears to me, tend to pick the center closest to their home. I would strongly recommend that you have your child's BMT done at either one of these centers--the response of FA patients to the BMT conditioning regime is very different from other patients, so you want to go to a center that specializes in BMT for FA.

Gene Therapy: A promising experimental therapy. Currently in the research phase, gene therapy involves trying to insert a normal copy of the affected FA gene into blood stem cells, thereby correcting the genetic defect. If successful, the normal gene will function and the blood stem cells will function like normal cells--resulting in blood counts returning to normal--and without the trauma associated with a bone marrow transplant. See the Gene Therapy page for more information on gene therapy research for fanconi anemia.

Genetics of Fanconi Anemia

Click on the link above to go to a page with more detailed information on the genetics of Fanconi Anemia.

Obtaining Publications

You will find references to this site to different articles from research journals. In some cases, you can read these articles online. However, in many cases, you need to go to a library or order the publication for delivery to you.

Click on the link above for information on how to obtain research publications that you will find referenced on this site, or from other sources. You can typically find any publication you want on the web and have it delivered directly to you.

Acrobat Reader
You'll encounter many publications (on this site and others) that can be viewed in Adobe's Portable Document Format (PDF format), which provides the capability for high resolution documents of professional quality. You need a browser plug-in to view PDF documents. The plug-in is called "Acrobat Reader" and is distributed for free by Adobe. You can obtain it by clicking on the graphic below:

Conclusion

This ends my page on general information on Fanconi Anemia. For more detailed information, I again refer you to the Fanconi Anemia Research Fund (FARF), Inc for more detailed and complete information.

My next page, genetics of fanconi anemia, in contrast to this page, is much more detailed regarding the genetics of FA and reproductive options.

Donate To Fanconi Anemia Research

You can donate to FA research at the Fanconi Anemia Research Fund (FARF), Inc website. Just click over to their page and scroll to the bottom, then click on the "Paypal donate" button at the bottom. Or, you can mail a check to the address given on the FARF webpage. Thank you.

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Last updated: 20 Dec 2004