What is Fanconi Anaemia?

Fanconi anaemia or FA, is a rare, inherited blood disorder where genes associated with DNA repair are faulty.

22 FA genes have been identified – all of which are involved in the DNA repair mechanism. Any mutations in DNA formed when cells divide or due to damage from UV or radiation cannot be repaired correctly. This can lead to a number of developmental abnormalities, bone marrow failure, leukemia and other cancers

The symptoms can range from almost nothing – where a person could go through their whole life without symptoms – to extreme.

Developmental Abnormalities

Many birth defects can be signs of FA, these include:

  • People with FA may have a short stature, ±60% of FA patient are affected.
  • Approximately 20% of FA patient have skeletal defects, these range from hip abnormalities, scoliosis an abnormal lateral curvature of the spine and spinal malformation.
  • Eyes are abnormally small and close-set. A visual defect known as Strabismus (a disorder of vision from normal orientation of one or both eyes so that both cannot be directed at the same point of focus). Epicanthic folds (a fold from the eyelids over the inner canthus of the eye)
  • Abnormal shaped ears, abnormal middle ear or deaf.
  • Neck abnormality known as Sprengel
  • Spine abnormality known as Spina bifida (a birth defect that involves the incomplete development of the spinal cord or its coverings)
  • Structural heart defects called Cardiopulmonary.
  • About 25% of FA patients suffer from kidney problems, being either deformed, missing or not in correct orientation.
  • Radii may be absent or hypoplastic (a condition of arrested development in which an organ or part remains below the normal size) the latter however is only present with a missing, oddly shaped, or three or more thumbs.
  • Alnae may is dysplastic (abnormal growth or development of cells, tissue, bone, or an organ.
  • Hands may be hypoplastic.
  • Gastrointestinal: Atresia (esophagus, duodenum, jejunum) imperforate anus, tracheoesophageal  fistula
  • Dislocation of hip (dislocation occurs when the ball–shaped head of the femur comes out of the cup–shaped acetabulum set in the pelvis)
  • Toe syndactyly (a hereditary disorder marked by the joining or webbing of two or more fingers or toes)

Developmental Problems

Other signs and symptoms of FA are related to physical and mental development. These include:

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

 Bone Marrow Failure

Bone marrow smear of a patient with chronic myelogenous leukemia.
Bone marrow smear of a patient with chronic myelogenous leukemia.

Bone marrow is the flexible tissue found in the interior of bones. Bone marrow produces new blood cells in large bones of the human body. The hematopoietic compartment of bone marrow produces approximately 500 billion blood cells per day, which enter the body’s blood circulation system.

In FA patients, 90% of patients develop bone marrow failure (aquired aplastic anaemia) by age 40.

When your bone marrow fails, it can’t make enough red blood cells, white blood cells and platelets.

With too few red blood cells (anaemia), less oxygen is carried to the body. This causes shortness of breath, dizziness, and headaches. The size of red blood cells can be much larger than normal (macrocytosis). This can impact their ability to carry oxygen efficiently.

With a low white blood cell count (neutropenia), you’re at risk of infections. Neutrophils are part of the immune system and help our bodies fight infection. Infections also may last longer and be more serious than normal for a FA patient.

Platelets help the blood to clot so when your platelet counts are low (thrombocytopenia), you may bleed and bruise easily, and suffer from internal bleeding. One symptom to look out for is petechiae. These are tiny red or purple spots on the skin that are caused by bleeding in small vessels under the skin.

Doctors diagnose aplastic anaemia using:

  • Family and medical histories and a physical examination.
  • A complete blood count (CBC) to check the number, size, and condition of your red blood cells. The CBC also checks numbers of white blood cells and platelets.
  • A reticulocyte count. This test counts the number of new red blood cells in your blood to see whether your bone marrow is making red blood cells at the proper rate.
  • Bone marrow tests. For a bone marrow aspiration, a small amount of liquid bone marrow is removed and tested to see whether it’s making enough blood cells. For a bone marrow biopsy, a small amount of bone marrow tissue is removed and tested to see whether it’s making enough blood cells.

Leukemia and other cancers

When bone marrow makes too many immature white blood cells called myeloblasts (often shortened to ”blasts”) it could predict acute myeloid leukemia (AML) – a type of blood cancer. Blasts don’t work correctly and should not be present in the blood. As the “blast” counts increase they crowd out and reduce the creation of healthy cells.

Cells that divide more frequently (like skin, blood and intestine cells) increase the risk for cancers.

Outlook

People who have FA have a greater risk than other people for some cancers. About 10 percent of people who have FA develop leukemia.

People who have FA and survive to adulthood are much more likely than others to develop cancerous solid tumours.

The risk of solid tumors increases with age in people who have FA. These tumors can develop in the mouth, tongue, throat, or esophagus. (The esophagus is the passage leading from the mouth to the stomach.)

Women who have FA are at much greater risk than other women of developing tumours in the reproductive organs.

FA is an unpredictable disease. The most common causes of death related to FA are bone marrow failure, leukaemia, and solid tumours.

Advances in care and treatment have improved the chances of surviving longer with FA. Blood and marrow stem cell transplant is the major advance in treatment. However, even with this treatment, the risk of some cancers is greater in people who have FA.