Rare but deadly: The genetic code and survival challenge of Fanconi anemia

Author: Han Bing, Chief Physician, Peking Union Medical College Hospital

Reviewer: Jiang Qian, Chief Physician, Third Medical Center, PLA General Hospital

Fanconi anemia is a rare hereditary bone marrow failure disease that not only causes abnormalities in bone marrow hematopoietic function, but is also accompanied by a series of non-hematological complications and is associated with a higher risk of tumors, posing a huge threat to patients' quality of life and long-term health.

The core challenge of this disease lies in the double blow of its hereditary nature and bone marrow failure. Under normal circumstances, the bone marrow, as the largest hematopoietic organ in the human body, continuously replicates and renews itself through hematopoietic stem cells to produce key blood cells such as red blood cells, white blood cells and platelets to maintain the normal physiological functions of the body. However, in patients with Fanconi anemia, this balance is broken.

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The intervention of genetic factors is the root cause of Fanconi anemia. The genes related to the growth and development of hematopoietic stem cells in the patient's body mutate. These genes involve DNA repair, DNA helix structure and other aspects, totaling more than 20 types. These gene mutations lead to the maldevelopment of hematopoietic stem cells and the inability to form normal lower-level mature cells, which in turn causes bone marrow failure. This hereditary bone marrow problem not only affects the production of blood cells, but also increases the patient's risk of tumors, including hematopoietic system tumors and non-hematopoietic system tumors, and its incidence is much higher than that of the general population.

The clinical manifestations of Fanconi anemia are extremely diverse, including both hematological manifestations and non-hematological symptoms, which is one of the important differences between it and other blood diseases. In terms of hematology, patients often show signs of blood cell reduction or bone marrow failure, such as anemia, leukopenia, and thrombocytopenia. Anemia may cause fatigue, palpitations, and memory loss in patients; leukopenia makes patients prone to infection or frequent fever; thrombocytopenia manifests as easy bleeding after a slight bump.

In addition to blood system abnormalities, Fanconi anemia is often accompanied by non-blood system growth and development disorders. Patients may have signs of microcephaly, growth retardation, mental retardation, etc. These characteristics often gradually appear during the patient's growth and development. In addition, internal organs may also be affected, such as pulmonary interstitial fibrosis, liver damage and fibrosis, further exacerbating the complexity of the disease.

It is worth noting that the clinical manifestations of Fanconi anemia do not appear overnight, but may gradually appear after the patient is born. Although the gene defect exists at birth, the appearance of clinical manifestations may be affected by many factors, including individual differences and environmental factors. Therefore, for suspected patients, continuous medical monitoring and evaluation are particularly important.

The diagnosis of Fanconi anemia requires a series of professional and meticulous examinations, including but not limited to blood cell counts, fetal hemoglobin level determination, chromosome breakage tests, and genetic testing. Despite certain false positive and false negative rates, chromosome breakage tests are still considered important indicators. Genetic testing is particularly critical for some cases, especially when the results of chromosome breakage tests are negative, genetic testing can provide additional evidence for diagnosis.

In clinical practice, it is particularly important to differentiate between Fanconi anemia and aplastic anemia. Although both are characterized by cytopenia, the former may be accompanied by abnormalities in other systems. For young patients with aplastic anemia, especially those with atypical symptoms or a family history, the possibility of Fanconi anemia should be considered, and corresponding chromosome breakage tests and gene screening should be performed. In addition, for patients who only show hematological abnormalities, they should also be alert to potential Fanconi anemia to avoid misdiagnosis.

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When facing Fanconi anemia, self-management and precautions of patients are equally important. Patients should pay close attention to their blood cell levels and other systemic manifestations and follow personalized treatment plans. Given that the risk of tumors in patients with this disease is significantly increased, regular follow-up and monitoring become necessary measures to enable early detection and intervention of problems such as tumors, infections, and organ dysfunction. In daily life, patients should follow the doctor's advice, take measures to prevent infection, avoid excessive fatigue, and maintain good living habits to slow the progression of the disease.

Bleeding is one of the common complications of Fanconi anemia, caused by thrombocytopenia. Once patients find signs of bleeding, they should seek medical attention immediately to control bleeding through platelet transfusions, the use of hemostatic drugs, etc., and check for other possible causes of bleeding. When bleeding first occurs, it is difficult for patients to accurately assess the severity, so they should follow the principle of "safety first" and seek professional medical advice in a timely manner.