Definition

Fanconi anemia is a rare inherited condition that impacts the bone marrow and various organs throughout the body. The bone marrow, situated within the central part of bones, normally produces stem cells, which mature into red blood cells, white blood cells, and platelets. However, in Fanconi anemia, the bone marrow fails to generate healthy blood cells, often leading to physical abnormalities affecting multiple organs.

This condition typically manifests early in life, with half of patients diagnosed before the age of 10, though around 10% are identified in adulthood. It affects both sexes equally and is observed across all ethnic groups. Globally, Fanconi anemia is extremely rare, occurring in only 1 in 160,000 individuals. Diagnosis commonly occurs during childhood or young adulthood.

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Causes

Fanconi anemia is an inherited genetic disorder resulting from mutations in a group of genes. There are approximately 23 known Fanconi anemia (FA) genes, and the condition can arise from mutations in at least 18 of these genes. These genes are crucial in safeguarding the body against DNA damage over time.

When mutations occur in FA genes, the proteins responsible for repairing DNA damage become impaired, hindering their ability to mend damaged DNA effectively. As a result, several consequences may arise:

• Continuous DNA damage leads to abnormal cell growth or cell death.
• Abnormal cell death can contribute to physical abnormalities and a reduction in the production of blood cells necessary for proper bodily function.
• Abnormal cell growth increasing the risk of developing blood cancers such as acute myeloid leukemia (AML) or other malignancies.

Risk factor

In most cases of fanconi anemia, both parents must carry mutations in the FA genes for the condition to manifest in their offspring. Typically, an affected individual inherits one copy of the abnormal gene mutation from each parent. If a child inherits one normal FA gene and one mutated copy, they become carriers of the disease but do not exhibit symptoms themselves. It's important to note that the risk of developing fanconi anemia is the same for males and females, with no gender predisposition.

Symptoms

Fanconi anemia can manifest with various symptoms and varying severity, which can differ among individuals. These symptoms may present from birth, childhood, or adulthood. Common manifestations include physical abnormalities, bone marrow failure, and an elevated risk of developing cancer or malignancies.

Physical abnormalities are often present from childhood, though in rare cases, they may only become apparent in adulthood. Approximately 60% of Fanconi anemia patients are born with at least one physical abnormality. Issues related to bone marrow failure and impaired blood production typically emerge when a child is between 6-8 years old. The increased risk of cancer predisposes patients to develop malignancies at a younger age.

Symptoms of Fanconi anemia can vary depending on the age of the individual.

In babies, approximately 75% of patients may exhibit the following symptoms:

• Low birth weight and short stature
• Abnormal birthmarks, which may appear dark or light
• Bone abnormalities, particularly missing thumb or radius bones in the lower arms
• Small eyes or heads
• Digestive issues
• Abnormalities of the kidneys, urinary tract, large intestine, or heart
• Male babies may have underdeveloped reproductive organs

As children age 6-8 years old, they may develop bone marrow failure, leading to decreased production of red blood cells, white blood cells, and platelets. Symptoms in children may include:

• Fatigue during daily activities
• Pale skin
• Frequent infections
• Easy bruising, nosebleeds, or bleeding gums
• Blood in urine or stool
• Growth failure or growth problems

Young adults with Fanconi anemia may primarily experience an increased risk of cancer. Symptoms vary widely among individuals, and some patients may only manifest symptoms in adulthood.

Diagnosis

Doctors typically diagnose Fanconi anemia while examining or treating medical conditions associated with the disease, such as cancer, progressive bone marrow failure, or congenital abnormalities.

During diagnosis, doctors inquire about the patient's symptoms and any relevant family medical history. They also review the patient's medical records, including past treatments. If further examination is deemed necessary, doctors may recommend various diagnostic tests, such as:

• Complete blood count: This test evaluates the health and activity of blood cells.
• Reticulocyte count: It measures the level of immature red blood cells in the bone marrow, assessing its ability to produce healthy red blood cells.
• Basic metabolic panel: This test provides information about the chemical balance and metabolism in the body.
• Bone marrow biopsy: A sample of bone marrow is taken for examination under a microscope.
• Imaging tests: These may include ultrasound or MRI scans.

Additionally, doctors may conduct genetic tests, including:

• Chromosome breakage test: This assesses how chromosomes in blood and skin cells react to certain chemicals.
• Genetic screening: It identifies specific gene mutations associated with Fanconi anemia.

Management

Generally, treatment focuses on managing blood disorders and medical conditions resulting from Fanconi anemia. Treatment options may include:

• Blood transfusions: These are used to provide deficient blood cells to patients.
• Bone marrow transplantation: This may be recommended to treat leukemia or bone marrow failure.
• Androgen therapy: This stimulates red blood cell production.
• Administration of synthetic growth factors: These help stimulate the bone marrow to produce more red and white blood cells.
• Surgical procedures: These may be necessary to correct physical abnormalities or organ damage.
• Treatment for cancer or malignancies.

Patients will require regular, long-term monitoring and treatment. This may involve annual blood and bone marrow examinations to monitor their condition. Additionally, examinations of vital organs such as the kidneys and heart may be conducted.

Complications

In patients with fanconi anemia, the bone marrow cannot produce healthy red blood cells, white blood cells, and platelets, leading to various symptoms and complications. Additionally, individuals with Fanconi anemia have an increased risk of developing various cancers, including:

• Acute myeloid leukemia (AML), is a type of blood cancer.
• Skin cancer.
• Head and neck cancer.
• Cancer affects other parts of the body.

Furthermore, Fanconi anemia can manifest with physical abnormalities that may affect organ function and alter an individual's appearance.

Prevention

Fanconi anemia is a congenital disorder, meaning individuals cannot reduce their risk of developing it. However, those with a family history of Fanconi anemia can undergo genetic testing to determine if they carry mutations in the FA genes. It's important to note that not all carriers of FA gene mutations exhibit symptoms, and not all carriers will pass these mutations to their offspring. Genetic testing can provide individuals with a comprehensive understanding of their genetic predisposition.

When to see a doctor?

If you notice fanconi anemia symptoms in your child, it's crucial to seek medical advice promptly. A doctor can conduct a thorough evaluation to identify the underlying cause of your child's symptoms.

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