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Fanconi Anemia: Causes, Symptoms, Diagnosis, Treatment

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Fanconi anemia (FA) is a rare, inherited failure of bone marrow, the spongy tissue in the center of bones, to produce sufficient blood cells. Normally, bone marrow stem cells produce red cells, white cells and platelets.

  • Red cells are the blood cells that carry oxygen to the body.
  • White cells are infection-fighting blood cells.
  • Platelets are disc-shaped cells that are necessary for blood clotting in response to injury.

A deficiency in producing red blood cells, the blood cells that carry oxygen to the body, is termed anemia. In FA, red blood cells may also be abnormally large, impairing their function.

Sometimes, the bone marrow will make immature white cells (myoblasts, usually called blasts) instead of healthy white cells. Blasts interfere with the production of normal blood cells.

Because of the failure of the bone marrow in FA, patients with the condition are at increased risk of developing leukemia, a type of blood cancer. Survivors to adulthood are more likely to develop solid tumors.

About 75 percent of children who inherit FA have birth defects, including abnormal pigment, short stature and irregularities of their thumbs.

Fanconi anemia

Who is at risk for Fanconi anemia (FA)?

About one person in 360,000 people in the United States is born with FA; one of every 300 is a carrier. Jews of Eastern European descent (Ashkenazi Jews) have a one in 90 chance of being a carrier, and one in 30,000 is born with it. The other ethnic group that has a higher risk is people native to South Africa.

What is the cause of Fanconi anemia (FA)?

At least 19 genes are known to be responsible for FA. Inheriting abnormal gene from both parents causes the disorder. With both parents having the same abnormal gene, the chance of a child inheriting FA is about 25 percent. People who inherit one copy of abnormal gene but don’t have FA can still pass the gene to their children.

What are signs and symptoms of Fanconi anemia (FA)?

  • Birth defects can be an early indicator. These may include abnormalities in the thumbs, such missing thumbs, more than two thumbs or oddly shaped thumbs.
  • Skin discoloration which may include café au lait spots (coffee-colored spots on the skin)
  • Unusually short stature, abnormal ears or kidney defects
  • Low birth weight and/or slow development
  • First sign of blood marrow failure: bruising and petechiae, or small purplish red spots caused by bleeding in vessels just underneath the skin. Fatigue from anemia is also common, as are infections due to an insufficient number of white blood cells being produced.
  • Other abnormalities of the head and face, neck, spine, eyes, ears, heart and lungs

Adults with FA can have underdeveloped sex organs. Women may start menstruating late, have difficulty becoming pregnant and start menopause sooner than women without FA.

How is Fanconi anemia (FA) diagnosed?

A genetic test is necessary to establish a diagnosis of FA. These tests include:

  • The chromosome breakage test, which treats white blood cells or sometimes skin cells with certain chemicals to see how the chromosomes in these cells react
  • Mutation screening, which looks for abnormalities in specific genes that are responsible for FA
  • If you have a family history of FA and become pregnant, the following two tests can determine whether the fetus has FA:
  • Amniocentesis, which tests chromosomes from a fluid sample of the amniotic sac (the fluid-filled sac around the fetus)
  • Chorionic villus sampling, in which a tissue sample taken from the placenta is tested for genetic defects related to FA

Newborns are examined for the birth defects previously mentioned.

Bone marrow failure is usually apparent by the second decade of life, although it can occur later. Aplastic anemia develops with failing bone marrow. Aplastic anemia is a disease in which the bone marrow cannot produce sufficient blood cells of all types. Therefore, your doctor will want to do a complete blood count (CBC). The CBC includes measures of:

  • Hemoglobin, the oxygen-carrying protein in red blood cells
  • Hematocrit, which is the volume of red blood cells in blood
  • Quantity (and size) of red blood cells
  • Quantity of white blood cells
  • Quantity of platelets

Low levels of any of these blood components may signal anemia.

A reticulocyte count, a measure of young red blood cells, may indicate that your bone marrow is not producing enough red blood cells.

Bone marrow aspiration (removing a small amount of the liquid portion of bone marrow through a needle) and a bone marrow biopsy (removing a small sample of bone marrow tissue through a needle) can confirm the diagnosis. If the number of cells in these samples is abnormally low, a diagnosis of aplastic anemia is established.

Ultrasound or magnetic resonance imaging (MRI) may be done to look at the size and location of the kidneys, to monitor for liver tumors and detect heart abnormalities.

What are the treatment options for Fanconi anemia (FA)?

Bone marrow transplant. If bone marrow failure has been diagnosed, or pre-leukemia or leukemia has occurred, a bone marrow transplant from a compatible related donor is the most effective treatment. For the majority of persons with FA, bone marrow transplantation is the ultimate therapy for marrow dysfunction.

Androgen therapy. Androgens are male hormones that can stimulate red blood cell production in anemias caused by a deficiency in red blood cell production. They can also enhance your platelet count but are less effective in producing white blood cells. If androgen therapy is chosen, ongoing treatment will be necessary.

Growth factors are naturally occurring substances in the body that stimulate the bone marrow to make more red and white blood cells. Synthetic versions of these substances may be used in patients with FA.

Surgery. Hand surgery early in life may improve function if FA has caused thumb abnormalities. Heart surgery may also be required for certain heart defects if they exist. Certain digestive problems, such as a defect in the area where the trachea meets the esophagus, may also require surgery.

What kind of ongoing medical care will a person with Fanconi anemia (FA) need?

You will need blood counts about every three months and occasional bone marrow examination. Stem cell transplants and transfusions will be needed depending on the results of these tests. If you have low levels of platelets, you may have to avoid certain activities that could cause bruising and bleeding.

The name Fanconi anemia can be misleading for both doctors and patients because the blood disorder aspect of FA are not the only problem for those with FA. Many things must be monitored, including hearing evaluation, assessment of endocrine system and GI tract issues, and long-term cancer surveillance because traits of FA could be very variable.

FA is a cancer-prone disorder. Close monitoring, especially for the high incidence of skin cancer, is important throughout the patient’s lifetime, even post-bone marrow transplant. The intrinsic genetic instability of FA cells means that exposure to ionizing radiation, environmental carcinogens, and chemotherapeutic agents likely poses special risks to persons with FA. Thus, tobacco and alcohol use may well have serious adverse consequences, even beyond those encountered in the general population.

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