Fanconi anemia or FA is a genetic disorder that results in bone marrow failure.
It is a recessive gene disorder. This means that in order for you to develop FA, your parents will both have to have the defective FA gene. The Fanconi Anemia Research Fund estimates that one in every 181 people has the defective gene (FARF). There is a one-in-131,000 chance of being born with FA. This condition can show up in men and women, and is seen more often in specific racial and ethnic groups.
Unfortunately, FA is very serious and has lifelong symptoms, which include:
Anemia is caused by a low red blood cell (RBC) count
Bone Marrow Failure
Bone marrow failure can lead to a number of types of anemia. RBCs and white blood cells (WBC), which are a key component to your immune system, are made in the bone marrow.
Birth defects connected to Fanconi anemia can include:
- bone or skeletal defects
- defects of the eye and ear (children with FA may be born deaf)
- skin discoloration
- kidney problems (such as a missing kidney)
- congenital heart defects, the most common of which is ventricular septal defect (VSD), a hole or defect in the lower wall that separates the left and right chambers of the heart
There are normally physical signs of this condition at birth, although some children with FA show no signs until later in life. According to the Fanconi Anemia Research Fund, more than 60 percent of patients born with FA have at least one physical anomaly. The median lifespan of FA patients is 29 years, although some patients live into their 50s (FARF).
By the time a child is 5 to 15 years old, the most common diagnoses associated with FA are acute myeloid leukemia (AML) and Myelodysplastic syndrome (Soulier, 2011). When individuals with FA become adults, they run a higher risk of contracting a wide range of cancers, including mouth and bone cancer.
FA is a genetic disease that is caused when two people with the recessive gene have children. “Recessive” means that the gene only expresses itself when it has been inherited from both parents. FA is a complicated genetic disease. Fifteen different genes have been connected to FA . According to the Fanconi Anemia Research Fund, abnormalities in those 15 genes account for 95 percent of FA cases (FARF).
Any child with a family history of FA is at risk for developing the condition. However, two ethnic groups are more likely than others to carry the recessive gene: Ashkenazi Jews and Afrikaners. Ashkenazi Jews are people of Eastern European Jewish descent, and Afrikaners are South Africans descended from Dutchmen who colonized South Africa in the 17th century.
FA is often diagnosed at birth or soon after. There are four categories of major conditions that can indicate that your child is suffering with FA:
Bone Marrow Failure
One of the major functions of bone marrow is to create red and white blood cells, and platelets (a type of blood cell involved in blood clotting). When the bone marrow fails, blood cell production begins to fall, leading to aplastic anemia. In addition, you will be more prone to infections, and it will take you longer to recover. Insufficient amounts of platelets will result in bleeding and bruising more than normal.
Blasts are abnormal white blood cells that interrupt the marrow’s production of blood cells. High amounts of blasts can result in acute myeloid leukemia (AML), a blood cancer.
This is a lack of energy due to low numbers of red blood cells, which help to oxygenate your blood. Signs of anemia include dizziness, headaches, and an inability to keep your hands and feet warm.
Certain types of birth defects will indicate that your infant has FA, including bone defects (thumb, arm), eye and ear defects, skin discoloration, kidney problems, and congenital heart defects.
These can include low birth weight, poor appetite, delayed growth, smaller than normal height, smaller than normal head size, and intellectual disability.
Symptoms in Adults
Adults who are diagnosed later in life will usually experience a completely different set of symptoms. Adult symptoms will usually affect the sexual organs or the reproductive system. Women will often have their periods later than normal, fertility issues, frequent miscarriages, early menopause, and smaller than normal genitals. In addition, men could experience fertility issues and have smaller than normal genitals.
One of the initial steps of diagnosis is investigating your family history. Since FA is caused by a recessive gene, parents might not be aware they are carriers. Doctors will look for a history of family illnesses such as anemia, digestive disorders, and immune problems.
FA is present in a child upon birth, even if he or she is born with no visible symptoms. If symptoms are not there at birth, they will normally show up between the ages of 2 and 15.
The symptoms of FA can look like symptoms of other conditions, and since FA is a genetic condition, genetic testing is the only reliable form of diagnosis. If your doctor believes your child might have FA, he or she will likely perform some form of genetic testing.
The methods used to conduct a genetic diagnosis of FA vary. The chromosome breakage test can be conducted by gathering either skin cells or blood. A chemical will be combined with the cells. The cells’ chromosomes are analyzed under the microscope. If the chromosomes show distinctive breakage, this indicates that the patient has FA.
Cytometric flow analysis (flow cytometry) will analyze skin cells by mixing them with chemicals. If your cells react to the chemicals, it means that you likely have FA.
Mutation screening consists of using a skin cell sample to look for any defects in the 15 known genes associated with FA.
Women who have a family history of FA should undergo genetic testing of their unborn baby. There are two ways to do this: amniocentesis and chorionic villus testing (CVS).
In amniocentesis, a doctor uses a needle to remove fluid from the amniotic sac that contains the unborn baby. The fluid is tested for the presence of FA genes.
The chorionic villus sample (CVS) test involves inserting a tube through the vagina and cervix, and using the tube to take tissue samples of the placenta. The tissue samples are then tested for the recessive FA gene. Chromosome breakage studies can also be performed on CVS.
If your child tests positive for the FA gene, he or she will be monitored for other signs of the condition. If, for example, the child is born with birth defects, the doctor will confirm an FA diagnosis with genetic testing.
FA is a genetic disease, and there is no absolute cure. However, the symptoms surrounding FA can be treated. The method of treatment for Fanconi anemia will vary based on the seriousness of the condition and the age of the patient.
Addressing anemia and other symptoms is the main focus of FA treatment. It is useful to look at treatment in terms of short-term and long-term strategies.
Short-term treatment methods could include:
- blood count checks to track the severity of the condition
- a yearly bone marrow test
- cancer/tumor screening
- antibiotics for any infections
- blood transfusions to increase blood cell count
Long-term treatment aims at offering an overall better quality of life and extending the lifespan of FA sufferers. It includes:
Blood and marrow stem cell transplant: In this procedure, stem cells are taken from a healthy donor (usually a family member) to replace the abnormal ones. The patient’s bone marrow is destroyed using radiation or chemotherapy. Then the new healthy marrow cells are injected into the bone, where they will grow and produce normal, healthy marrow and blood cells.
Androgen therapy: This treatment uses male hormones on an ongoing basis to increase the long-term production of blood cells.
Synthetic growth factors: Man-made or naturally-occurring growth substances can assist your body in making more blood cells.
Surgery: Surgery may be able to correct birth defects that occur in the arms, thumbs, hips, and other body parts.
Fanconi anemia is a serious, life-threatening disease. Although the median age of survivors is 29, improvements in blood and bone marrow stem cell transplants have increased the odds of a longer life. The National Heart Lung and Blood Institute suggests that patients or parents of patients find support groups, because the disease can be a challenge for all family members. Despite the seriousness of the disease, new treatments are being worked on that show promise (NHLBI, 2009).