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Fanconi Anemia

Fanconi anemia, or FA, is a rare, inherited blood disorder that leads to bone marrow failure. The disorder is inherited in an autosomal recessive manner, which means two copies of a faulty gene (one from each parent) are required to cause the disease. At least 13 faulty genes are associated with FA. People who have only one copy of a faulty FA gene are FA "carriers." Carriers don't have the disorder, but they can pass the faulty gene to their children.

In the United States and Europe, about 1 out of every 300 people is an FA carrier. This carrier rate leads to 1 in 360,000 people being born with FA.

Symptoms

Your doctor may suspect you or your child has Fanconi anemia (FA) if you have signs and symptoms of:

  • Anemia
  • Bone marrow failure
  • Birth defects
  • Developmental or eating problems

Because FA is an inherited disorder, children may be tested if one of their brothers or sisters has FA.

Anemia

The most common symptom of anemia is fatigue (feeling tired or weak). If you have anemia, it may seem hard to find the energy to do normal activities. Other symptoms include shortness of breath, dizziness, headache, coldness in the hands and feet, pale skin, and chest pain.

Bone Marrow Failure

When your bone marrow fails, it can't make enough of the three types of blood cells that your body needs to work normally: red blood cells, white blood cells, and platelets. This can cause many problems that have various signs and symptoms.

With too few red blood cells, you can develop anemia. In FA, the size of your red blood cells also can be much larger than normal. This makes it harder for these cells to work well.

With too few white blood cells, you're at risk for infections. Infections may last longer and be more serious than in people who don't have FA.

With too few platelets, you may bleed and bruise easily, suffer from internal bleeding, or have petechiae. Petechiae are tiny red spots caused by bleeding in small blood vessels just below your skin.

In some people who have FA, the bone marrow makes a lot of harmful, immature white blood cells called blasts. These blasts don't work like normal blood cells. As they build up in the bone marrow, they block the production of normal blood cells. A large number of blasts in the bone marrow can lead to a type of blood cancer called acute myeloid leukemia (AML).

Birth Defects

Many birth defects can be signs of FA. These include:

  • Bone or skeleton defects. FA can cause missing, oddly shaped, or three or more thumbs. Arm bones, hips, legs, hands, and toes may not form fully or normally. The spine may be curved, a condition called scoliosis.
  • Eye and ear defects. The eyes, eyelids, and ears may not be normally shaped. A child also may be born deaf.
  • Skin discoloration. This includes coffee-colored areas or odd-looking patches of lighter skin.
  • Kidney problems. A child might be born with a missing kidney or kidneys that aren't shaped normally.
  • Congenital heart defects. The most common congenital heart defect linked to FA is a ventricular septal defect (VSD). VSD is a condition in which the wall that separates the heart's lower chambers (the ventricles) is deformed or has a hole in it.
Developmental Problems

Other signs and symptoms of FA are related to physical and mental development. These include:

  • Low birth weight
  • Poor appetite
  • Delayed growth
  • Below-average height
  • Small head size
  • Mental retardation or learning disabilities
Signs and Symptoms of Fanconi Anemia in Adults

Some signs and symptoms of FA may develop as you or your child gets older. Women who have FA may experience some or all of the following:

  • Sex organs that are less developed than normal
  • Menstruating later than women who don't have FA
  • Starting menopause earlier than women who don't have FA
  • Problems getting pregnant and carrying a pregnancy to full term

Men who have FA may have sex organs that are less developed than normal. They also may be less fertile than men who don't have the disease.

Diagnosis

The signs and symptoms of FA aren't unique to the disease. They're also linked to many other diseases and conditions, such as aplastic anemia. For this reason, genetic testing is needed to confirm a diagnosis of FA. Genetic tests for FA include the following.

Chromosome Breakage Test

This is the most common test for FA. It's available only in special laboratories (labs). It shows whether your chromosomes (long chains of genes) break more easily than normal.

Sometimes, skin cells are used for the test, but usually a small amount of blood is taken from a vein in your arm using a needle. A technician combines some of the blood cells with certain chemicals.

If you have FA, the chromosomes in your blood sample break and rearrange when mixed with the test chemicals. This doesn't happen in the cells of people who don't have FA.

Cytometric Flow Analysis

Cytometric flow analysis, or CFA, is done in a lab. This test examines how chemicals affect your chromosomes as your cells grow and divide. Skin cells are used for this test.

A technician mixes the skin cells with chemicals that can cause the chromosomes in those cells to act abnormally. If you have FA, your cells are much more sensitive to these chemicals. The chromosomes in your skin cells will break at a high rate during the test. This doesn't happen in the cells of people who don't have FA.

Mutation Screening

A mutation is an abnormal change in a gene or genes. Geneticists and other specialists can examine your genes, usually using a sample of your skin cells. With special equipment and lab processes, they can look for gene mutations that are linked to FA.

Treatment

Blood and Marrow Stem Cell Transplant

A blood and marrow stem cell transplant is the current standard treatment for patients who have FA that's causing major bone marrow failure. Healthy stem cells from another person, called a donor, are used to replace the faulty cells in your bone marrow.

If you're going to receive stem cells from another person, your doctor will want to find a donor whose stem cells match yours as closely as possible.

Stem cell transplant is most successful in younger people who:

  • Have few or no serious health problems
  • Receive stem cells from a brother or sister who is a good donor match
  • Have had few or no previous blood transfusions

During the transplant, you'll get donated stem cells in a procedure that's like a blood transfusion. Once the new stem cells are in your body, they travel to your bone marrow and begin making new blood cells.

A successful stem cell transplant will allow your body to make enough of all three types of blood cells to work normally. However, even if you've had a stem cell transplant to treat FA, you'll still be at risk for some types of blood cancer and cancerous solid tumors. Your doctor will check your health regularly and often after the procedure.

Androgen Therapy

Before improvements made stem cell transplants more effective, androgen therapy was the standard treatment for people who had FA. Androgens are artificial male hormones that can help your body make more blood cells for long periods.

Androgens are effective at increasing your red blood cell and platelet counts. They don't work as well at increasing your white blood cell count.

Unlike a stem cell transplant, androgens don't allow your bone marrow to make enough of all three types of blood cells on its own. You may need ongoing treatment with androgens to control the effects of FA. Also, over time, androgens lose their ability to help your body make more blood cells, which means you'll need other treatments.

Androgen therapy can have serious side effects, such as liver disease. This treatment also can't prevent you from developing leukemia (a type of blood cancer).

Synthetic Growth Factors

Your doctor may choose to treat your FA with growth factors. These are substances found in your body, but they also can be man-made.

Growth factors help your body make more red and white blood cells. Growth factors that can help your body make more platelets are still being researched.

More studies are needed on growth factor treatment for FA. Early results suggest that growth factors may have fewer and less serious side effects than androgens.

Gene Therapy

Researchers are looking for ways to replace faulty FA genes with normal, healthy genes. They believe that the replacement genes will be able to make the proteins needed to repair and protect your bone marrow cells. Early results hold promise, but this form of treatment for FA is still in the experimental stage.

Surgery

Surgery may be needed to improve the use of arms, thumbs, hips, legs, and other parts of the body that aren't formed right because of birth defects caused by FA.

If your child is born with a ventricular septal defect—a hole in the wall that separates the lower chambers of the heart—he or she may need surgery to close the hole so the heart can work properly.

Children who have FA also may need surgery to correct digestive system problems that can harm their nutrition, growth, and survival.

One of the most common problems is an FA-related birth defect in which the trachea (windpipe), which carries air to the lungs, is connected to the esophagus, which carries food to the stomach.

This can cause serious breathing, swallowing, and eating problems and can lead to lung infections. Surgery is needed to separate the two organs to allow normal eating and breathing.

 

Source

National Heart, Lung, and Blood Institute, USA.