Fanconi anemia type 3

Fanconi Anemia Type 3

Fanconi anemia (FA) is a rare genetic disorder that leads to bone marrow failure, congenital abnormalities, and increased cancer risk. It is part of a group of diseases known as the Fanconi anemia complementation groups, each caused by mutations in different genes. Fanconi anemia type 3, also known as FA-A, is one of the most common subtypes and is caused by mutations in the FANCA gene.

Genetics

Fanconi anemia type 3 is inherited in an autosomal recessive manner. This means that an individual must inherit two copies of the mutated FANCA gene, one from each parent, to manifest the disease. The FANCA gene is located on chromosome 16 and is responsible for encoding a protein that is part of the Fanconi anemia core complex. This complex is crucial for the repair of DNA interstrand crosslinks, which are a type of DNA damage.

Pathophysiology

The FANCA protein, along with other proteins in the Fanconi anemia pathway, plays a critical role in the repair of DNA damage. When the FANCA gene is mutated, the repair process is disrupted, leading to the accumulation of DNA damage. This results in the characteristic features of Fanconi anemia, including bone marrow failure, congenital abnormalities, and increased susceptibility to cancers, particularly acute myeloid leukemia and squamous cell carcinoma.

Clinical Features

Individuals with Fanconi anemia type 3 may present with a variety of clinical features, including:

• Bone Marrow Failure: This is the most common and serious complication, leading to pancytopenia, which is a reduction in red blood cells, white blood cells, and platelets.
• Congenital Abnormalities: These may include skeletal anomalies, such as thumb and radial defects, short stature, and developmental delays.
• Increased Cancer Risk: Patients have a higher risk of developing certain cancers, particularly hematologic malignancies and solid tumors.

Diagnosis

Diagnosis of Fanconi anemia type 3 involves a combination of clinical evaluation, family history, and genetic testing. Chromosomal breakage tests using diepoxybutane (DEB) or mitomycin C (MMC) are commonly used to identify increased chromosomal fragility, a hallmark of FA. Genetic testing can confirm the diagnosis by identifying mutations in the FANCA gene.

Management

Management of Fanconi anemia type 3 is multidisciplinary and includes:

• Hematopoietic Stem Cell Transplantation (HSCT): This is the only curative treatment for bone marrow failure in FA patients.
• Androgen Therapy: May be used to stimulate blood cell production in some patients.
• Supportive Care: Includes regular monitoring, blood transfusions, and treatment of infections.
• Cancer Surveillance: Due to the increased risk of cancer, regular screening and early intervention are crucial.

Prognosis

The prognosis for individuals with Fanconi anemia type 3 varies depending on the severity of the disease and the success of treatments such as HSCT. Early diagnosis and management can improve outcomes, but the risk of cancer remains a significant concern.

Also see

• Fanconi anemia
• Bone marrow failure
• DNA repair
• Genetic disorders