Fanconi anemia is a rare genetic syndrome, involving failure of the bone marrow to produce blood cells.
Fanconi anemia (FA) is a rare genetic * syndrome, involving failure of the bone marrow * to produce blood cells. FA is a premalignant medical disorder, which means that individuals with FA often eventually develop some form of cancer. However, the most common cause of death among people with FA is bone marrow failure leading to a life-threatening anemia * . FA patients often have various characteristic birth defects and other medical problems in addition to the anemia and cancer.
The cells that make up blood include red blood cells that carry oxygen to body tissues, white blood cells that function as part of the immune system * to fight off infections, and platelets, which are necessary for blood clotting and wound closure. Each blood component is critical to maintaining life. Bone marrow has an essential role in the production of mature blood cells. FA involves a type of anemia known as aplastic anemia, in which all three types of blood cells are deficient due to bone marrow failure. Having a deficiency in such critical body components leads to many different medical problems that can be life threatening.
FA is an autosomal recessive genetic disorder. Autosomal recessive disorders are diseases in which both parents must be carriers of the gene in order for their child to inherit the condition. If both parents are carriers, there is a 25 percent risk for the child to be affected by the disease. There are at least 13 known genes * that can be mutated (changed) and cause FA. Only one of these 13 genes is needed to cause the disease. The proteins expressed by these genes may cause DNA * damage that affects bodily processes such as blood production by the bone marrow and causes cancer. However, the exact mechanism by which these gene mutations cause birth defects, bone marrow failure, and cancer was not known as of 2015.
In the United States, 1 in 300 individuals carries the mutated genes that can cause FA. About 1 in 360,000 people in the United States are born with the disease. In the United States, the Ashkenazi Jewish population has a higher rate of 1 carrier per 90 people and 1 case per 30,000 people. In other countries, FA occurs at similar rates. Certain ethnic groups have higher rates of carrying the FA genes. These groups include sub-Saharan African people and Spanish gypsies.
FA is a genetic disorder caused by mutations in one of 13 different genes, but how this mutation happens was not known as of 2015. The cells affected by these mutated genes may be more susceptible to environmental factors that cause cancers, or the cells may not have the self-protective mechanism that healthy cells have.
Babies born with FA typically have low birth weight. Three-fourths of all people with FA have visible birth defects, too. Areas of altered skin pigment, known as café au lait spots because of their light brown color, are characteristic. Many children with FA are short and have small heads. They may also have abnormal thumbs, eyes, and ears, along with impaired sight and hearing. Multiple internal organs may also be defective, such as the kidneys, gastrointestinal tract (often esophagus, small intestine, or anus), heart, or lungs.
As children with FA continue to grow, bruises and small blood hemorrhages under the skin may be the first sign of blood problems associated with aplastic anemia and suggest platelet * deficiency. These individuals have pale skin and tire easily, which is caused by red blood cell deficiency and decreased oxygen delivery to tissues. Frequent infections are caused by white blood cell deficiency.
The combination of obvious birth defects and blood disorders indicates FA. In one-fourth of FA patients, a diagnosis of FA only occurs after leukemia * or some other form of cancer is discovered. DNA tests can detect mutations in the known FA genes.
FA patients are often treated by a team of physicians, each of whom may address a different aspect of the disease. Treating the aplastic anemia may call for a bone marrow transplant. If appropriate bone marrow is not available, blood transfusions * may be performed to replenish blood cells needed by the body. Specific drugs that enhance blood cell production may also be prescribed. These drugs cannot correct the problem, but they may help reduce symptoms. For example, some drugs can help reduce bleeding. Blood counts are performed at least every three months, and bone marrow examination is necessary at least once per year. Sometimes surgery can help correct certain birth defects.
Having FA makes a person likely to develop many kinds of cancer, even after bone marrow transplantation. People with FA often develop leukemia, a cancer originating in blood cells. The type of leukemia most often associated with FA is called acute myelogenous leukemia (AML), which is characterized by a rapid and unhealthy increase in immature white blood cells that cannot be used by the body to fight infection.
The accumulating immature cells replace the normal bone marrow as well as the normal blood cells and are cancerous. This condition is life threatening. AML progresses rapidly and is typically fatal within weeks or months if left untreated. Other types of cancer associated with FA are characterized by tumors of the head and neck or tumors of the esophagus, reproductive tract, brain, liver, kidney, and lung.
FA is a fatal disorder if left untreated and is sometimes fatal at an early age even with treatment. If a patient undergoes a bone marrow transplant along with other supportive treatments and has any severe birth defects corrected in a manner that sustains the person's life, then the prognosis is improved. With the best medical care and circumstances, a person with FA may live about 30 years. Making a diagnosis of FA early in the course of the disease improves the prognosis, as well as early cancer detection. However, the quality of life may be severely affected by frequent medical tests and procedures, complications such as birth defects or cancer, and various possible physical limitations.
See also Anemia, Bleeding, and Clotting • Genetic Diseases: Overview
Briggs, Bill, and Diane Mapes. “‘Can't Sit and Wait’: Gene Therapy Trial Aims to Cure Rare Fanconi Anemia.” Fred Hutch News Service. June 22, 2015. https://www.fredhutch.org/en/news/centernews/2015/06/Gene_therapy_aims_to_cure_Fanconi_Anemia.html (accessed December 5, 2015).
Genetics Home Reference. “Fanconi Anemia.” National Institutes of Health. http://ghr.nlm.nih.gov/condition/fanconi-anemia (accessed December 5, 2015).
The Rockefeller University. “Fanconi Anemia Mutation Database.” http://www.rockefeller.edu/fanconi/ (accessed December 5, 2015).
Fanconi Anemia Research Fund. 1801 Willamette St., Suite 200, Eugene, OR 97401. Toll-free: 888-326-2664. Website: http://www.fanconi.org (accessed December 5, 2015).
National Heart, Lung, and Blood Institute. PO Box 30105, Bethesda, MD 20824-0105. Telephone: 301-592-8573. Website http://www.nhlbi.nih.gov (accessed December 5, 2015).
* bone marrow is the soft tissue inside bones where blood cells are made.
* genetic (juh-NEH-tik) refers to heredity and the ways in which genes control the development and maintenance of organisms.
* anemia (uh-NEE-me-uh) is a blood condition in which there is a decreased hemoglobin in the blood and, usually, fewer than normal numbers of red blood cells.
* immune system (im-YOON SIStem) is the system of the body composed of specialized cells and the substances they produce that helps protect the body against disease-causing germs.
* genes (JEENS) are chemical structures composed of deoxyribonucleic acid (DNA) that help determine a person's body structure and physical characteristics. Inherited from a person's parents, genes are contained in the chromosomes found in the body's cells.
* DNA, or deoxyribonucleic acid (dee-OX-see-ry-bo-nyoo-klay-ik AH-sid), is the specialized chemical substance that contains the genetic code necessary to build and maintain the structures and functions of living organisms.
* platelets (PLATE-lets) are tiny disk-shaped particles within the blood that play an important role in clotting.
* leukemia (loo-KEE-me-uh) is a form of cancer characterized by the body's uncontrolled production of abnormal white blood cells.
* blood transfusions (trans-FYOOzhunz) are procedures in which blood or certain parts of blood (such as specific cells) are given to a person who needs them due to illness or blood loss.