Fanconi anemia (FA) is a rare, inherited disease primarily affecting children. While the outcome for people with FA tends to be poor, researchers predict that newer molecular and gene therapies can help improve quality of life.
Fanconi anemia is the result of inherited abnormalities in certain genes, which
This article discusses what Fanconi anemia is, its symptoms and treatments, and how researchers are working with molecular and gene therapies to help improve FA outcomes in the near future.
Fanconi anemia (FA) is a
FA is the result of a defect, or mutation, in one of the 23 known FA genes. There is currently no cure for FA, but treatments can help relieve symptoms and extend a person’s lifespan.
Fanconi anemia is an extremely rare disease. About 31 children are born with FA per year in the United States, according to the Fanconi Anemia Research Fund. The incidence rate, or the likelihood of a child being born with FA, is about
The number of people with FA globally is unknown. Researchers estimate that the incidence of people carrying an abnormality in an FA gene in the United States is
FA can have a wide range of effects on all systems of the body. The types and severity of symptoms vary widely among individuals. Symptoms usually become noticeable by age 10.
The three main characteristics of FA are:
- Congenital abnormalities: About
75%of people with FA have physical anomalies at birth. The most common ones include:
- short height
- structural abnormalities, commonly in the thumb and arm
- skeletal abnormalities, commonly in the hips, spine, or ribs
- small reproductive organs in males
- kidney structural issues
- café au lait spots in the skin
- small head
- widely spaced or crossed eyes
- Progressive bone marrow failure: Bone marrow stem cells that produce all three types of blood cells usually begin to fail by age 10. As blood cell counts diminish, disorders such as anemia or low red blood cell count, leukopenia or low white blood cell count, and thrombocytopenia (low platelet count) often develop. Symptoms may include:
- frequent infections
- spontaneous bleeding from mucous membranes
- easy bruising
- difficulty breathing
- extreme fatigue
- Increase in cancer risk: People with FA have a higher risk of certain cancers in early adulthood, especially acute myeloid leukemia and squamous cell carcinoma.
Fanconi anemia results from a mutation in any of the 23 known FA genes.
FA is a recessive genetic disorder. This means that for a child to be born with FA, both parents have a mutation in one of the 23 known FA genes, and the child inherits the mutated gene from both parents. Each child of these parents has a 25% chance of this happening.
Many subtypes of FA exist, according to which FA genes are involved. Genetic testing is used to determine the specific genes. FA genes are on the DNA repair pathway, which means the abnormal FA gene limits the body’s ability to repair DNA.
In recent years, researchers have explored the molecular basis of FA, focusing on energy metabolism. This has led some
FA diagnosis is confirmed via clinical evaluation, a detailed health history, and specialized tests.
The main diagnostic test for FA is a chromosome breakage test, which examines a sample of a person’s blood for chromosome breakage, the hallmark symptom of FA. This is why FA
Other tests for FA may include:
- blood tests to determine levels of red blood cells, white blood cells, and platelets
- X-ray tests to examine any skeletal malformations or internal structural anomalies
- molecular genetic testing to determine which genes are mutated
FA treatment focuses on relieving the specific symptoms a person has, which vary greatly depending on their age, health, and type of FA.
A coordinated team approach is usually necessary. For example, a healthcare team can include pediatricians, surgeons, cardiologists, kidney specialists, gastroenterologists, and hearing and eye specialists.
Here are some FA treatment options:
- Blood and bone marrow stem cell transplant: FA treatment involving blood and bone marrow stem cell transplant is standard for people with bone marrow failure. It is the only treatment that may cure the blood aspects of FA.
- Blood transfusion: A blood transfusion can provide supportive treatment but is not curative.
- Androgen therapy: Man-made male hormones
can sometimesimprove stem cell growth and increase red blood cell and platelet counts, but it is also supportive and not curative.
- Growth factor supplementation: Natural or man-made growth substances can help bone marrow cells make more red and white blood cells.
- Gene therapy: There is proposed testing for replacing an abnormal gene with a normal gene in clinical trials. The correct gene could make proteins that would repair and protect bone marrow cells. The correction of CD34+ in affected cells is now feasible, according to research.
- New oral medication: Clinical trials are testing new drugs for FA. For example, Stanford Medicine Children’s Health recently received FDA approval for a proposed clinical trial to test whether a drug called an ALDH activator may be able to restore standard function to stem cells in people with FA.
- Surgery: Various types of surgery may help correct skeletal malformations, heart defects, and internal abnormalities
- Chemotherapy and radiation: If cancer develops, these standard treatments can cause greater toxicity in people with FA. Centers experienced in treating FA are usually recommended.
Below are some commonly asked questions on FA:
Is Fanconi anemia life threatening?
FA is a life-limiting disorder. This means that the disease leads to conditions that may be fatal.
Progressive bone marrow failure used to be the main cause of death in people with FA. Currently, with an increase in stem cell transplant success, the most frequent cause of death is squamous cell carcinoma.
The rapid pace of current research into targeted molecular therapy and gene therapy will likely lead to an increase in longevity and quality of life for people with FA in the near future.
At what age is Fanconi anemia diagnosed?
Diagnosis of FA usually occurs when symptoms first develop. Symptoms such as blood abnormalities can occur between 6 to 8 years old, and bone marrow failure symptoms can vary.
For about 10% of people with FA, diagnosis does not occur until adulthood because symptoms do not appear until then.
What is the life expectancy of someone with Fanconi anemia?
Fanconi anemia is a rare genetic disease that leads to blood marrow failure and a wide array of other symptoms affecting multiple systems and organs in the body. It results from mutations in any of 23 known FA genes. It is an inherited disease that is passed down through families.
There is currently no cure for FA, although there are treatments that help manage symptoms and extend longevity. Currently, the average lifespan is around 22 years. With treatment, some people with FA live into middle age and beyond.
Researchers are exploring possible treatments involving targeted molecular therapy and gene therapy. Progress is rapid, and researchers predict new treatments will become available in the near future.