Fanconi anemia comprises inherited disorders where the body fails to produce a crucial DNA-protecting protein, leading to impaired bone marrow function.
This deficiency results in insufficient production of various blood cells, causing oxygen deficiency, abnormal bone and organ development, and developmental delay. Inadequate red blood cells cause oxygen shortage, while reduced white blood cells increase vulnerability to infections and cancer. Decreased platelets hinder blood clotting after injuries. Individuals with Fanconi anemia often have physical abnormalities at birth, such as short stature, finger malformations, skin discoloration, kidney and eye issues, and skeletal irregularities. However, 25 to 40% may lack visible abnormalities and are diagnosed in childhood due to low blood cell counts, hearing loss, developmental delays, or cancer caused by bone marrow failure. The inability to repair DNA damage elevates cancer risk, with leukemia often appearing early. Other cancers like head and neck tumors, esophageal, cervical, vulvar, or liver cancers may also occur prematurely due to this condition.
Fanconi anemia type A currently has no cure, and treatment involves monitoring and managing symptoms as they arise. Some individuals can improve blood cell counts temporarily with medication, although resistance often develops over time. Bone marrow transplantation can cure associated leukemia, but patients are highly sensitive to the required chemotherapy and radiation, making them potentially unsuitable candidates. Transplants also do not prevent solid tumors, necessitating chemotherapy and radiation for treatment.
Fanconi anemia type A is caused by pathogenic (disease-causing) variants in the FANCA gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Sephardic Jewish descent have a 1 in 133 chance to be a carrier.
Resources:
Revised October 2023
