Fanconi anemia (FA) is a rare genetic disorder that affects 1 in 160,000 people. This condition causes progressive bone marrow failure in about 90% of affected people. Bone marrow is the spongy material inside bones that makes platelets, red blood cells, and white blood cells. These cells are important for good health.
Fanconi anemia is a disease that affects many parts of the body, often causing physical abnormalities, such as deformed thumbs or forearms, as well as organ defects, such as missing kidneys and heart defects.It also increases the chance of developing certain cancers, such as leukemia (blood cancer) and myelodysplasia (bone marrow disease).
This article will review common symptoms of FA, along with causes and risk factors, how to diagnose the condition, and treatment options.
What are the symptoms of Fanconi anemia?
Fanconi anemia (FA) is a rare genetic disorder that causes progressive bone marrow failure. In most cases, signs and symptoms of Fanconi anemia appear at birth or in early childhood, between the ages of 5 and 10 years.
As the bone marrow loses its ability to make blood cells and platelets, it can cause low blood cell counts – a condition called aplastic anemia. Low blood counts and bone marrow failure may cause the following symptoms:
- extreme fatigue
- frequent infections
- easy bruising
- bleeding from the nose or gums
These symptoms are due to low numbers of red blood cells, white blood cells, or platelets. About 75% of children with FA are born with one or more of the following physical characteristics:
- Cafe Spots (light brown birthmarks)
- short and small
- Thumb and arm abnormalities (missing, deformed, or redundant thumb or underdeveloped/missing forearm bone)
- low birth weight
- small head or eyes
- Kidney, genital, gastrointestinal, cardiac, and central nervous system abnormalities
- curved spine (Scoliosis)
- internal bleeding
- congenital (at birth) heart defect
About 60% of people experience one of the following nonphysical symptoms:
- Learning disabilities (problems) or intellectual disabilities
- Poor appetite
- Delayed growth and puberty
Causes and Risk Factors
Fanconi anemia (FA) is a genetic disorder passed on from generation to generation. Although the exact cause of FA is unknown, defects in at least 18 genes that help the body repair certain types of DNA damage are associated with the disease.
An estimated 80%–90% of FA cases are associated with mutations in one of three genes: FANCA, FANCC, and FANCG.
considered in most cases Autosomal recessive inheritance, which means a child must receive two copies of the mutated gene—one from each biological parent—to develop the disease. People with one mutated gene will be carriers (able to pass the mutated gene to their children), but usually will not develop symptoms.
FA is more common than the general population in Ashkenazi Jewish descent, Hispanic Roma, and black South Africans.
What you should know about genetic testing
How to Diagnose Fanconi Anemia
The diagnosis of Fanconi anemia (FA) is based on a thorough physical examination, detailed patient history, and various specialized blood tests.
The most common test for FA is a blood test called chromosome breakage test. This test looks for DNA damage that characterizes FA. If FA is a concern, this test can be done in utero (before the child is born).
For patients with symptoms, a healthcare provider will take your medical history, ask about your symptoms and any family history of similar illnesses, and perform a focused physical exam looking for dark spots called café-au-lait spots and any physical abnormalities. They will also order a complete blood count (CBC).
If FA is suspected, healthcare providers may also order an electrocardiogram (EKG), which can detect abnormal heart rhythms that may indicate a heart defect. CT examination (CT) scan or Magnetic Resonance Imaging (MRI) may show defects in the body or organs, including:
- Abnormalities of the thumb and arm, such as extra or misshapen or missing thumb and fingers, or an underdeveloped or missing radius bone (one of the forearm bones)
- Bone abnormalities in the hip, spine, or ribs
- Structural kidney defect or lack of kidney
- male reproductive organs
- Tissue defects in isolated hearts
The wide variability of symptoms in patients with FA makes accurate diagnosis based on clinical presentation alone difficult.
To determine the extent of disease in an individual diagnosed with FA, the following evaluations are recommended as needed:
- Ultrasound of the kidneys and urinary tract
- formal hearing test
- developmental assessment
- Referral to necessary specialists as needed
how to treat this condition
Treatment of Fanconi anemia (FA) is based on low or abnormal blood counts and the age of the patient.
Treatment is also designed to manage your symptoms, which may require input from multiple specialists, including Pediatriciansurgeon, cardiologist (cardiologist), Nephrologist (nephrologist), urologist (Urinary Tract Specialist), gastroenterologist (Gastroenterologist), Hematologist (Blood Specialist), Audiologist and ENT doctor (specialists who assess and treat hearing problems), ophthalmologist (ophthalmologists) and other healthcare professionals.
The following short-term strategies to monitor disease and control symptoms are critical for the treatment of FA:
- regular blood counts
- annual bone marrow examination
- Screening for tumors and cancer
- Antibiotic treatment (to fight infection) as needed
- Blood transfusions as needed (to increase blood cell counts)
Long-term treatment can include:
- Blood and bone marrow stem cell transplantation
- Surgery to correct birth defects
- Gene therapy
- Genetic testing and counseling
The following long-term treatments are also commonly used in patients with FA to increase blood counts:
- used for androgens (Androgens): Androgens improve blood counts in about 50% of people with FA. The earliest responses appear in red blood cells, and increases in hemoglobin usually occur within the first or two months of treatment. The response of white blood cell count and platelet count is variable.
- hematopoiesis Growth Factors: Treating Patients With granulocyte Colony stimulating factor (G-CSF) has been shown to increase neutrophils (a type of white blood cell) in some people, but it is not as commonly used as androgen therapy.
- Hematopoietic Stem Cell Transplantation (HSCT): This treatment involves taking donor stem cells from a peripheral (external) source such as bone marrow or blood or umbilical cord blood and placing them in the bone marrow. It is the only curative therapy for hematological (blood-based) manifestations of FA.
What are bone marrow stimulators used for?
What is the prognosis?
A better understanding of the genetic and molecular causes of FA and improved clinical management have transformed the condition from a fatal disease to a chronic condition that can be well managed with lifelong multidisciplinary therapy.
While the average life expectancy for people with this condition is between 20 and 30 years, some patients live in their 30s, 40s and 50s.
A person’s prognosis depends largely on the progression of their bone marrow failure and whether they go on to develop aplastic anemia. It is also important to monitor the presence of associated cancers, such as acute myeloid leukemia and myelodysplasia, for early detection and treatment.
Blood and bone marrow stem cell transplantation has been shown to be an effective treatment, but as patients with Fanconi anemia age, the risk of developing solid tumors increases, necessitating lifetime screening for these cancers.
Fanconi anemia (FA) is a rare genetic disorder that can be passed from generation to generation. People with this disorder usually inherit one mutated gene from each of their parents. They may be born with physical abnormalities, such as extra or misshapen or missing thumbs and fingers, underdeveloped or misshapen forearms, or heart defects.
Most FA cases are diagnosed before or shortly after birth. In some cases, symptoms may appear later, usually between the ages of 5 and 10. Symptoms may include fatigue, easy bruising, and bleeding gums due to low blood counts.
Diagnosis usually involves genetic testing and other blood tests. Imaging studies can also be used. Treating FA is a life-long battle that requires careful monitoring. Fortunately, treatment options have advanced, and many people with FA are able to live fulfilling lives.
The treatment of Fanconi anemia has greatly improved due to advances in modern medicine, but it still requires lifelong monitoring, including blood counts every three months and occasional bone marrow examinations.
Lifestyle changes are encouraged early in life, such as avoiding certain activities that can cause bruising and bleeding (if you have low platelet levels), avoiding smoking and drinking alcohol to limit your cancer risk, and often become a natural lifelong habit for many people with FA .