Fanconi's anemia is distinct from Fanconi's syndrome, a rare kidney disorder in which nutrients are lost through the urine.

Fanconi's anemia is inherited in an autosomal recessive fashion, thus one copy of an abnormal gene is passed on by each parent. It occurs in all racial and ethnic groups. It is classically diagnosed between 2 and 15 years of age.

The disease is caused by a genetic defect that prevents cells from fixing damaged DNA or removing toxic, oxygen-free radicals that damage cells. Patients may be suspected of having the disease, if they have particular birth defects or develop decreased blood counts.

This set of physical abnormalities occur in 80% of the cases:

• Skin pigment change -- darkened areas of the skin, cafe-au-lait spots, vitiligo
• Short stature
• Upper limb anomalies -- missing, extra or misshapen thumbs; underdeveloped or absent radius bone in the forearm; anomalies of the hands; abnormalities of the ulna
• Small testicles, genital changes
• Other skeletal anomalies -- congenital hip abnormality, scoliosis, spinal or rib malformations, small head
• Eye/eyelid anomalies
• Kidney malformations
• Ear anomalies/deafness
• Hip, leg, and toe abnormalities
• Gastrointestinal/cardiopulmonary malformations

Other potential symptoms:

• Mental retardation
• Learning disability
• Low birth weight
• Failure to thrive
• An affected sibling

Common tests performed for evaluation of Fanconi's anemia include:

• CBC (complete blood count) initially demonstrates low platelets. (thrombocytopenia), then low neutrophils (a type of white blood cell), and finally low hemoglobin (anemia), which develops over months to years.
• Bone marrow biopsy.
• Clastogenic stress-induced chromosomal breakage analysis on blood cells of patients and their siblings to diagnose the disease. Here, chemotherapy is added to a blood sample to check for abnormal damage to chromosomes.
• HLA tissue typing on the patient and their family members to determine if any are matching bone marrow donors.
• Hand X-ray, and other imaging studies (X-ray, CT scan, MRI) to evaluate any anomalies.
• Hearing test.
• Developmental assessment.
• Ultrasound of the kidneys.
• Amniocentesis or chorionic villous sampling has been used for prenatal diagnosis.

If the hematological changes are mild to moderate and the patient does not require transfusions, a period of observation is currently recommended with frequent blood count checks and yearly bone marrow examinations. Observations for the development of secondary malignancies are also performed. In the short term, growth factors (such as erythropoetin, G-CSF, and GM-CSF) can be used to improve blood counts. Other growth factors for platelet stimulation are currently under investigation.

Bone marrow transplantation can cure the blood count problems associated with Fanconi's anemia. A HLA matched sibling is the best donor source, although umbilical cord blood cells and unrelated bone marrow can also be used. This therapy is very effective, and although there are associated toxicities, there has been improvement in the care of Fanconi patients during the transplant. There is approximately a 70% success rate for those patients fortunate enough to have a donor.

Even though a successful bone marrow transplant can cure the bone marrow problems from Fanconi's anemia, patients are at risk for other cancers and must be regularly followed by a physician (see below).

Prior to bone marrow transplantation, androgen therapy (oxymetholone, nandrolone decanoate) combined with low doses of steroids (hydrocortisone, prednisone) was the standard treatment, and this approach is currently used if the patient does not have an appropriate bone marrow donor. Typically, 50-75% of patients initially respond to androgen therapy, however, all patients will rapidly relapse when the drug is stopped. In most cases, these drugs eventually become ineffective.

Symptoms due to low blood counts, such as bleeding, infections, or symptomatic anemia (fatigue, shortness of breath, chest pain, dizziness), are treated with transfusions or antibiotics as needed. Patients with low neutrophil counts, who develop a fever, are usually treated with intravenous antibiotics.

Most patients visit a hematologist, an endocrinologist, and an ophthalmologist regularly. An orthopedist, gynecologist, or nephrologist may be seen as needed.

The reported survival of patients with Fanconi's anemia is highly varied, ranging from 2 to 25 years. The prognosis is especially poor if blood counts are low. Survival has likely been improved with the development and refinement of therapies, such as bone marrow transplantation.

Although bone marrow transplantation can restore blood counts, patients with Fanconi's anemia remain predisposed to a variety of cancers (leukemia, myelodysplastic syndrome, liver cancer, and others).

Women with Fanconi's anemia who become pregnant should be closely followed by a physician as they often require transfusions throughout pregnancy. Fertility is decreased in males, although a small number of Fanconi patients have fathered children.

Fanconi's anemia is an inherited disorder, and little can be done to prevent the disease short of genetic counseling for families known to be affected as a result. However, some complications, such as pneumococcal pneumonia, hepatitis, and varicella infections, can be prevented by vaccination.

Additionally, patients should avoid known carcinogens and undergo regular cancer screening to detect malignancies early in their course, should they arise.