Fanconi Anemia Health Article

Definition

Fanconi anemia is an inherited disorder characterized by a severe form of anemia and various other physical malformations. Patients with Fanconi anemia are susceptible to various types of cancer.

Description

Fanconi anemia (FA) was first described in 1927 by a Swiss pediatrician named Guido Fanconi. It is a rare, inherited form of aplastic anemia. Aplastic anemia is a life-threatening condition in which a person is unable to produce adequate amounts of red blood cells, white blood cells, or platelets. Red blood cells serve to carry oxygen to all areas of the body. White blood cells help to fight infection and disease. Platelets are responsible for clotting to help to heal wounds and control bleeding. Without adequate amounts of these important blood cells, patients affected with aplastic anemia are easily fatigued and susceptible to infections. Most cases of aplastic anemia develop throughout the course of a person's lifetime. However, in FA, the aplastic anemia is inherited, or present from birth.

FA is also associated with various other findings. These include short stature, skeletal abnormalities, kidney problems, and heart defects. Additionally, people with FA experience a high incidence of leukemia and an increased incidence of other types of cancer.

The chromosomes in the cells of FA patients break and rearrange easily. Chromosomes are the information manuals of our cells. Genes are arranged on chromosomes in a linear fashion, like beads are arranged on a string. Genes tell our cells how to make proteins. These proteins perform many vital functions in the body. When chromosomes break, genes are disrupted and they do not function correctly. This leads to abnormal proteins and various health problems. The chromosome breakage in FA can be seen in the laboratory and is used to diagnose the disorder.

Genetic profile

It has been determined that at least eight different genes are associated with FA. A change in any one of these genes causes the disorder. The proteins made by these genes are not yet known and their role in FA is not yet understood.

For someone to be affected with FA, each of their parents must have a defect in the same gene. Parents that carry the defective gene do not show symptoms of FA because they have a corresponding gene on the other chromosome that produces an adequate amount of protein. Thus, they often do not know they are carriers until they have an affected child. If both parents carry the same defective gene, each pregnancy has a 25% chance of inheriting both abnormal genes and being affected with FA. Likewise, each pregnancy has a 25% chance of inheriting two functional copies of the gene and being unaffected. This leaves a 50% chance that the pregnancy will have one functional gene and one defective gene and will be an unaffected carrier of the disorder. This pattern is known as autosomal recessive inheritance.

The FA genes are designated by a letter of the alphabet. Defects in the FA-A gene account for approximately 65% of FA cases. Defects in the FA-C gene account for about 15% of FA cases. In the Ashkenazi Jewish population, however, defects in this particular gene are responsible for nearly all cases of FA.

Demographics

FA occurs equally in males and females. The total number of FA patients has not been documented. It has been estimated, however, that between one in 100 and one in 600 people carry one of the defective genes. FA is found in all ethnic groups but is more frequent in the Ashkenazi Jewish population. One in every 89 people in this population carry a mutation in the FA-C gene.

Signs and symptoms

The signs and symptoms of FA generally appear between the ages of three and 12. In rare cases, symptoms do not present until adulthood. These symptoms vary in severity from case-to-case. Even within a family, siblings who are both affected may show very different signs of the disorder.

Aplastic anemia is the first sign of FA in many patients. In some cases, it may be the only sign of the

disorder. In aplastic anemia, the bone marrow does not produce an adequate amount of red cells, white cells, or platelets. This can lead to several conditions. Anemia can result due to the deficiency in red blood cells, leading to weakness, fatigue, and a pale appearance. Without enough white blood cells, the patient may be vulnerable to common germs and infections. The deficiency in platelets can cause easy bruising, nosebleeds, and possible internal bleeding.

Ten to fifteen percent of patients with FA develop leukemia, specifically acute myelogenous leukemia (AML). Leukemia is a cancer of the blood system in which abnormal white blood cells grow rapidly in number and suppress the development of healthy blood cells. AML is a particularly aggressive type of leukemia and is difficult to treat successfully. Individuals with FA are very sensitive to the toxic drugs used to fight leukemia, which makes treatment even more difficult.

Among the physical defects associated with FA, short stature is very common. Additionally, an affected child may be born with missing, misshapen, or extra thumbs, or an underdeveloped or missing bone in the arm. Approximately one-fifth of patients with FA exhibit other skeletal abnormalities, such as those of the hip, spine, or rib. About 25% of individuals with FA are born with abnormalities of the kidneys. Some are born with defects of the heart, stomach, esophagus, or intestinal tract. These problems may require immediate surgery at birth.

FA is also associated with hyperpigmentation, or a darkening of the skin, in approximately 65% of patients. This darkening may be present in the form of spots or it may be more diffuse over a larger portion of the body. Additionally, the head or eyes might be smaller than average and some patients may not grow properly. Learning disabilities are thought to be fairly common in FA as well. Hearing loss has been reported in 10% of patients.

As these individuals become older, other problems may result. In males, it is common to see underdeveloped male organs and infertility. Females often have a delay in the start of their menstrual periods and a decrease in fertility. Menopause may occur as early as age 30.

People with FA, especially those over the age of 20, are at a high risk to develop cancerous tumors in the head, neck, intestines, urinary tract, liver, and esophagus. Women are also at an increased risk for cancers of the reproductive tract.