Fanconi anemia

Red cells form in the bone marrow; When there is a decrease in hematopoietic tissue, which is what gives rise to the different blood cells, including red blood cells, and there is no tumor, fibrosis or other type of process that occupies the space of the bone marrow, it is spoken of a process of aplasia, that is, a lack of production of the precursor cells that give rise to red blood cells, leukocytes and platelets. When the patient suffering from aplastic anemia also suffers from bone malformations, skin alterations and some other type of malformation, it is likely that he or she suffers from Fanconi anemia.

How is it produced?

Fanconi anemia was first described by the Swiss pediatrician Guido Fanconi in 1927. It is a congenital aplastic anemia of autosomal recessive inheritance in which various genes related to DNA repair capacity are involved. Given the great cellular production that it produces in the bone marrow, it is normal for it to be affected if these types of genes are altered.

In Fanconi anemia, 15 different genes are involved, the FANC genes, expressed on different chromosomes, all autosomes except in the case of FANCB, which is expressed on the X chromosome, hence 2% of anemia cases of Fanconi have an X-linked inheritance.

It is not a frequent disease, it affects 1 in 350,000 people, hence it is considered a rare disease.

Symptoms

Patients with Fanconi anemia are often underweight and short at birth. Bone malformations and alterations are frequent, especially at the level of the thumbs, which can be deformed, absent or have some supernumerary. Radius alterations are also frequent, which can present malformations or be absent. Other less frequent bone alterations occur in the spine and hips.

Other common manifestations are cutaneous, these patients frequently having coffee-with-milk spots, or skin hyperpigmentation. Likewise, patients with Fanconi anemia may have microcephaly and their eyes may also be smaller than usual.

Nor is it unusual for them to suffer from congenital malformations at the kidney level (even with the lack of one of the two kidneys at birth), cardiac or gastrointestinal malformations, and mental retardation.

The symptoms of anemia usually appear around 5-10 years, with the symptoms of an anemic syndrome, namely, pale skin and mucous membranes, asthenia, dyspnea, palpitations, headache, lack of concentration, irritability or insomnia, all consequences from poor tissue oxygenation.

Likewise, due to the failures in the other cell lines, that of leukocytes or white blood cells and that of platelets, the patient often suffers from recurrent infections and bleeding processes.

Patients with Fanconi anemia are also prone to other hematologic abnormalities, such as myelodysplastic or syndromes, as well as head and neck, esophagus, and gynecologic tumors.

Diagnosis

The diagnosis will be based on the questioning of the patient and laboratory data. It is convenient to detect symptoms of tiredness, paleness, dyspnea, headache or other neurological disorders. Likewise, the existence of recurrent infections or bleeding episodes and the exposure to possible causative agents such as drugs, toxic substances, radiation or infections by certain viruses should be investigated. A full examination will be performed to search for common skin lesions and bone malformations.

If anemia is suspected, a complete blood test will be performed, which should include a complete blood count, basic biochemistry, and reticulocytes. Characteristically, the red cells of aplastic anemia are larger than usual but contain a normal amount of hemoglobin; This is assessed with specific parameters, which are the mean corpuscular volume (MCV), which assesses the mean size of the red cells, and the mean corpuscular hemoglobin (HCM), which measures the mean amount of hemoglobin per red cell. Since there is an increase in MCV and a normal HCM, it is classified as a macrocytic anemia (larger cells) normochromic (normal amount of hemoglobin).

Likewise, a decrease in both the number of leukocytes and platelets will be appreciated, unless it is a selective aplasia of the red line.

The reticulocytes in the blood will also be evaluated, that is, the young forms of red cells existing in the blood, which in this case will be diminished, since the bone marrow is the affected tissue and cannot create new red cells.

The confirmatory test of aplastic anemia is provided by the bone marrow biopsy, which would allow studying the red cells in formation as well as the other cell lines and it will be seen that there is a decrease in the cells that form in it. Aplastic anemia is considered severe when the bone marrow cell occupancy is less than 30% and when, in addition, in the blood test, there are neutrophils below 500 per mm3, platelets below 20,000 per mm3 or reticulocytes below 1%.

In any case, to accurately diagnose Fanconi anemia as a cause of aplastic anemia, even if it exists and the malformations of the disease occur, the leukocytes from a sample of the patient's blood must be subjected to exposure to substances like mitomycin C that break DNA strands. The chromosomes of patients with Fanconi anemia are broken in a characteristic way.

Treatment

Between 50% and 70% of patients with Fanconi anemia may respond to treatment with androgens and hematopoietic growth factors, but eventually the marrow stops responding to these stimuli.

The treatment of choice to solve the spinal aplasia of Fanconi anemia is bone marrow transplantation, which will cure 80% of cases, obtaining the cells for transplantation either from a compatible relative, from the umbilical cord or from an external donor.

Precautionary measures

Since it is a congenital disease, there are no specific preventive measures to prevent Fanconi disease. In the event that a relative suffers from it, it is important that their immediate relatives undergo a study to rule out that they have it or are carriers of it.