Fanconi anaemia is a rare genetic disorder that affects various parts of the body, including the bone marrow, leading to organ defects, an increased risk of certain cancers, and physical abnormalities. This article will focus on how Fanconi anaemia impacts the bone marrow, causing several haematological disorders and manifestations.

What is fanconi anaemia?

Fanconi anaemia is a genetic disorder passed down through families in an autosomal recessive pattern. This means that to be affected by this disease, a child has to inherit the faulty gene from both parents. The hallmark of this condition is progressive bone marrow failure, which leads to decreased production of all blood cell types (red cells, white cells, and platelets), a condition called pancytopaenia. This occurs because, in Fanconi anaemia, the mutations impair the cells' ability to repair DNA damage, causing bone marrow function to fail.^1,2

Several abnormalities can be caused by Fanconi anaemia besides bone marrow abnormalities. These abnormalities include:^3,4

• Short stature
• Skeletal abnormalities of the ribs and spine
• Irregular skin
• Malformed thumbs or forearms
• Malformed kidney
• Defects of the urinary tract
• Heart defects
• Kidney structural problems
• Gastrointestinal problem
• Abnormal genitalia and reproductive system abnormalities
• Nervous system abnormalities, etc. 

Bone marrow failure

Bone marrow is like a factory for blood cells. Its function is to produce new blood cells, including red blood cells, white blood cells, and platelets. Red blood cells (erythrocytes) are responsible for carrying oxygen to all body parts, while white blood cells (leucocytes) help protect the body from infections. Platelets (thrombocytes) play a role in blood clotting to stop bleeding.

In Fanconi anaemia, there are mutations in the genes that impair your cells’ ability to repair DNA damage, leading to bone marrow failure. When this happens, the blood cell production is also affected. You may experience extreme tiredness due to low red blood cells (anaemia), increased susceptibility to infections because of a low white blood cell count, and problems with blood clotting due to low platelet levels.^1,5

Specific blood cell concerns

Anaemia

Anaemia in Fanconi anaemia is characterised by a deficiency of red blood cells, which are essential for transporting oxygen to all parts of your body. When there is a shortage of these cells, tissues receive less oxygen, leading to symptoms such as:^1,6

• Fatigue – your energy to do normal activities may decrease significantly
• Shortness of breath, especially during physical exertion, because your body struggles to get enough oxygen
• Dizziness
• Headache
• Pale skin and mucous membranes

Leukopaenia

When your white blood cell count is low, your immune system is weakened, making it harder to fight infections. This is called leukopaenia. People with Fanconi anaemia are at an increased risk of developing serious infections, particularly if they also have a decrease in a specific type of white blood cell called neutrophils. Symptoms that may present include:^1,6

• Recurrent bacterial/viral/fungal infections
• Fever and malaise
• Prolonged illness and a delayed healing process

Thrombocytopaenia

When there’s damage to a blood vessel that leads to bleeding, platelets move to the site and help close the wound through a process called hemostasis. However, proper clotting requires a normal platelet count. If the platelet count is too low, a condition known as thrombocytopenia, you may experience problems with blood clotting. This issue is common in people with Fanconi anaemia. Symptoms of thrombocytopaenia include:^1,6

• Increased risk of bleeding and prolonged bleeding: Even minor injuries can lead to excessive bleeding
• Easy bruising: Bruises may occur from minor impacts or injuries
• Petechiae: Small purple or red spots on the skin caused by bleeding from capillaries

Increased risk of leukaemia

Individuals with Fanconi anaemia have an increased risk of developing several types of cancer, including:⁷

• Leukaemia, mainly acute myeloid leukaemia (AML)
• Head and neck cancer
• Oesophageal cancer
• Vulvar cancer
• Liver cancer 

We will further discuss leukaemia, a cancer that affects your blood.

In Fanconi Anaemia, mutations in certain genes affect how well DNA repairs itself. This leads to genomic instability, making it harder for cells to maintain their structure and increasing the chance of genetic changes during cell division. As a result, cells may start growing uncontrollably, which is a common sign of cancer. Hence, patients with Fanconi anaemia are at a higher risk for various types of cancer, including leukaemia.

Leukaemia is a type of cancer that affects both the blood and the bone marrow. Here are the types of leukaemia based on the affected cell and disease progression: 

• Acute lymphoblastic leukaemia (ALL) 
• Acute myeloid leukaemia (AML)
• Chronic lymphocytic leukaemia (CLL)
•  Chronic myelogenous leukaemia, also called chronic myeloid leukaemia (CML) 

Acute myeloid leukaemia (AML) is a fast-growing type of blood cancer and one of the most common cancers in Fanconi anaemia. It happens when there are changes in the chromosomes within cells, causing these cells to mutate. These changes lead to the production of too many immature white blood cells, called myeloblasts, which do not function properly. AML progresses quickly and is especially common in children.⁷

Symptoms of acute myeloid leukaemia include:^8,9

• Fever
• Lethargy (feeling drowsy, tired)
• Bleeding
• Enlargement of the liver
• Lymphadenopathy (inflammation or swelling of lymph nodes)
• Musculoskeletal symptoms
• Anaemia-related symptoms such as shortness of breath
• Bleeding and easy bruising, nosebleeds, and gum bleeding (all symptoms that are related to low platelets)
• Weight loss

Treatment and management

Management of Fanconi anaemia involves several approaches aimed at addressing the various issues it causes, including haematological problems and preventing complications.

Supportive therapy

• Blood transfusions: To maintain adequate levels of red blood cells and platelets
• Antibiotics or antifungals: To prevent or treat infections due to a weakened immune system

Haematopoietic stem cell transplantation

Haematopoietic stem cell transplantation replaces damaged bone marrow with healthy stem cells from a compatible donor, usually a matched sibling. It is the primary choice to treat bone marrow failure patients who present with Fanconi anaemia.

Androgen therapy

If a transplant isn’t possible, some patients may be treated with androgen therapy, which helps boost the production of blood cells. While it does not cure the disease, androgen therapy can improve blood cell counts.

Surgery

Surgery is usually performed to correct structural deformities or for patients who develop cancer.

Gene therapy

In gene therapy, the abnormal gene causing the disorder is replaced with a normal gene, aiming to correct the underlying genetic defect.^1,10

FAQs

What are the blood findings for Fanconi anaemia?

In a complete blood count (CBC), you may find pancytopenia, which includes low red blood cells, low white blood cells, and low platelets.

What is the triad of Fanconi anaemia?

1. Haematological abnormalities
2. Physical malformations
3. Increased risk of cancer

What are the spots on Fanconi anaemia?

These are areas of skin hypopigmentation, usually presenting as light-colored flat patches or, most commonly, hyperpigmentation, patches which are darker than the surrounding skin (also known as café-au-lait spots).

What is a reticulocyte count in Fanconi anaemia?

Reticulocyte count means a number of immature red blood cells in the blood. This number shows the capacity of the bone marrow in red blood cell production

Summary

Fanconi anaemia (FA) is a condition that causes bone marrow failure, physical differences, and a higher risk of cancer. It happens because of a mutation in genes that normally help repair damaged DNA. These mutations lead to an impaired ability of cells to repair damaged DNA, causing genomic instability. Haematological manifestations of Fanconi anaemia include: 

• Anaemia (low red blood cells)

Symptoms: shortness of breath, fatigue, and dizziness.

• Leukopaenia (low white blood cells)

Symptoms: weakened immune system that causes a higher risk of infections.

• Thrombocytopaenia (low platelets)

Symptoms: easy bruising and bleeding. 

• Leukaemia, especially acute myeloid leukaemia (AML)

Symptoms: Fever, feeling drowsy, bleeding, weight loss, enlargement of the liver, swelling of lymph nodes, anaemia-related symptoms such as shortness of breath, thrombocytopaenia-related symptoms such as easy bruising or bleeding, nosebleed, and bleeding gums.