Fanconi Anemia

Alternative names: Fanconi's Anemia, FA

Fanconi anemia is a rare, inherited blood disorder that leads to bone marrow failure.  As a result, insufficient new blood cells are produced, as well as many faulty blood cells in some cases.

Fanconi anemia can affect many organs and tissues, and in children can cause birth defects, developmental problems and other serious health issues.

Discovered by Guido Fanconi in 1927, FA is the most frequently reported rare inherited bone marrow failure syndrome.  At the time of writing, some 2,000 cases have been reported in medical literature.

Incidence; Causes and Development

Fanconi's anemia affects both genders roughly equally.  In the United States, about 1 out of every 181 people is an FA carrier (this does not mean they have the disease).  This carrier rate leads to about 1 in 130,000 people being born with FA.  It accounts for approximately 25% aplastic anemia cases.

FA occurs in all races and ethnic groups, but two ethnic groups – Ashkenazi Jews and Afrikaners – are more likely FA or be carriers.

Fanconi anemia is an inherited disease which occurs when both parents pass the same faulty gene to their child.

Signs and Symptoms

Adult women who have Fanconi anemia may have some or all of the following signs and symptoms:

• Underdeveloped sex organs
• Delayed onset of menstruation
• Early onset of menopause
• Difficulty becoming pregnant
• Increased risk of miscarriage

Men with FA may also have underdeveloped sex organs and be less fertile.

However, FA is usually detected during childhood.  Signs and symptoms include:

• Anemia, which causes fatigue, lack of energy, shortness of breath, dizziness, headaches, coldness in the hands and feet, pale skin, and chest pain.
• Bone marrow failure
• Birth defects
• Developmental or eating problems

Approximately 75% of patients with Fanconi anemia have major birth defects, which include:

• Bone or skeleton defects almost anywhere in the body – bones that are underdeveloped or abnormal
• Eye and ear defects – for example, abnormal shape, deafness
• Odd-looking dark or light patches of skin
• Missing or malformed kidneys
• Congenital heart defects, particularly a ventricular septal defect, which is a hole or defect in the lower part of the heart wall

Developmental problems include:

• Low birth weight
• Poor appetite
• Delayed growth
• Below-average height
• Small head size
• Mental retardation
• Learning disabilities

Diagnosis and Tests

Most people with this disorder are diagnosed between the ages of 2 and 15 years.  A knowledge of medical and family history is important but, because FA has a lot in common with other diseases, only genetic testing can confirm the diagnosis.

The advent of molecular diagnostics has greatly improved the accuracy of Fanconi anemia diagnosis.

Diagnostic testing can include:

• Chromosome Breakage Test
• Cytometric Flow Analysis
• Mutation Screening

Treatment and Prevention

Medical advances – in particular blood and marrow stem cell transplant – have improved the chances of surviving longer with FA.  Long-term treatments treat the anemia by replacing damaged bone marrow cells with healthy ones that can make enough blood cells.

The four main types of long-term treatment are:

• Blood and marrow stem cell transplant
• Androgen therapy
• Synthetic growth factors
• Gene therapy

Other treatments simply attempt to improve quality of life by using medicines that help the body make more blood cells in the short term.

Surgery can repair some birth defects.

Frequent blood count checks are often recommended, as well as annual bone marrow tests and cancer screening.

Prognosis; Complications

Without treatment the average lifespan for people who have Fanconi's anemia is 20-30 years, with the most common causes of death being bone marrow failure, leukemia, and solid tumors.  However, modern treatment of aplastic anemia with medications, blood products, and stem cell transplantation has increased life expectancy beyond this range.

It is estimated that 9% of patients developed leukemia, of which 95% develop acute myeloid leukemia (AML) – usually rare in children.  In other words, AML risk is some 500 times higher than normal.  In the majority of cases, leukemia develops between the ages of 15 and 35 years, with 13% being affected by age 50 years.

Myelodysplastic syndrome has been reported in 7% of FA patients, which is 5,000 times the normal incidence.

Possible complications of Fanconi anemia include hemorrhages, infections, leukemia, myelodysplastic syndrome, liver tumors, and other cancers.

About 10% of people who have Fanconi anemia develop leukemia.  In these people, the bone marrow makes a lot of immature and potentially dangerous white blood cells called blasts.  Blasts don't work normally, but instead build up and prevent the bone marrow from making enough normal blood cells.  A large build-up of blasts in the bone marrow can lead to acute myeloid leukemia (AML).

FA sufferers who survive to adulthood have a 40-fold increased risk of developing cancerous solid tumors, and this risk increases with age.  By age 50, 30% of FA patients have developed solid tumors, which usually develop in the mouth, tongue, throat, or esophagus but can also occur as tumors of the vulva/vagina, brain, skin, cervix, breast, kidney, lung, lymph nodes, stomach, and colon.  Women with FA are at much higher risk of developing reproductive organ tumors, with the risk for vulvar/vaginal squamous cell carcinoma being approximately 3,000 times normal.