Diamond-Blackfang anemia

The anemia of Diamond-Blackfen is the most famous form of partial red cell aplasia in children. The disease was named after the authors who described in 1938 four children with characteristic signs of the disease.

A total of more than 500 cases of Diamond-Blackfang anemia have been reported, the frequency of the syndrome is estimated as 4-10 cases per 1,000,000 births, the ratio of boys and girls is about 1: 1. Family cases account for 10-20% of all cases of Diamond-Blackfang anemia, including the disease was diagnosed in monozygotic twins. Proved as autosomal dominant, and autosomal recessive path of inheritance. 80-90% of cases of Diamond-Blackfen anemia are diagnosed during the first year of life, and in 25% of the patients anemia is detected already at the time of birth. The diagnosis of Diamond-Blackhead anemia in older children should be made with caution, after the exclusion of the acquired forms of PKAA. Approximately 25-30% of cases of Diamond-Blackplet anemia are associated with a mutation of the S19 ribosomal protein gene, the significance of which is unknown for erythropoiesis. Another chromosomal locus associated with the development of the disease is 8p22-p23.

[1], [2], [3]

Causes and pathogenesis

The Diamond-Blackfang anemia is a hereditary disease with a presumably autosomal recessive type of inheritance, with the same frequency among the patients there are boys and girls. Among the mechanisms of development of the disease indicate an anomaly of erythroid progenitor cells, a defect in their microenvironment in the bone marrow, cell-mediated suppression and the presence of humoral erythropoiesis inhibitors. The permanent signs of the disease include a decrease in the number of erythroid units in the bone marrow, an increase in the level of erythropoietins in the blood, a defect in additional bone marrow cells.

[4], [5], [6], [7], [8], [9], [10]

Symptoms of Diemond-Blackfen Anemia

Symptoms are limited to pallor and other symptoms of severe anemia. Enlargement of the liver and spleen is not characteristic of the disease, but later as a result of the formation of fibrosis and / or cirrhosis of the liver as a result of iron overload and the course of posttransfusion hepatitis B and C, hepatosplenomegaly becomes a typical symptom.

For patients with Diamond-Blackfang anemia, congenital developmental anomalies are characteristic, but their spectrum and severity differ significantly from Fanconi anemia. Characteristic is also the chronic course of Diamond-Blackhead anemia; a part of patients, more often in pubertal period, note spontaneous remission. Anemia of Diamond-Blackfen - predlekemicemic syndrome: AML developed in at least 8 patients.

Diagnostics

Diagnostic criteria for Diamond-Blackhead anemia:

• normochromic, often macrocytic anemia;
• deep reticulocytopenia;
• normocellular bone marrow with an isolated decrease in the content of erythroid progenitors;
• normal or slightly reduced number of granulocytes;
• normal or slightly elevated number of platelets.

The level of fetal hemoglobin, although it can be increased, does not serve as a diagnostic sign. Rarely in patients with Diamond-Blackfang anemia, the number of primitive erythroblasts that can be taken for leukemia blasts is increased in the bone marrow from the first months of life, leading to erroneous diagnosis of leukemia. With age, the cellularity of the bone marrow, determined by trepanobiopsy, can be significantly reduced, in some patients, moderate thrombocytopenia develops. Specialized studies allow us to reveal a sharply reduced number of committed erythropoiesis precursors-burst-forming units of erythrocytes and colony-forming units of erythrocytes. The level of erythropoietin in patients with Diamond-Blackfang anemia is sharply increased.

To differentiate the anemia of Diamond-Blackfen is necessary from other forms of PKAA in children, mainly from TED. Documentation of the normal level of hemoglobin before the clinical manifestation of anemia and independent resolution of the syndrome testify against Diamond-Blackkemia anemia.

[11], [12], [13]

Treatment for Diemond-Blackfen Anemia

The only effective group of drugs in the treatment of Diamond-Blackhead anemia are glucocorticosteroids. Usually, treatment is started with prednisolone inside at a dose of 2 mg / kg per day. Reticulocyte response is expected in 2 weeks, followed by an increase in hemoglobin. After the release of hemoglobin values on the plateau, the dose of prednisolone should be gradually reduced to a minimum, allowing to maintain a hemoglobin level above 90 g / l. Often, to maintain a hematologic response, it is sufficient to use doses in the region of 2.5-5 mg per day or every other day. If a standard dose of prednisolone is not answered, it is justified to use higher doses - 5 mg / kg per day. Elevated doses can be used in the pulse-therapy regime for 7 days followed by a 2-week break. A total of 3-4 pulse-therapy. When the answer is reached, you can either increase the intervals between courses, or transfer the patient to a daily intake of glucocorticosteroids in standard doses, followed by a reduction to minimally effective doses. The use of ultra-high doses of methylprednisolone - 30-100 mg / kg, despite its relative popularity, has not proved its high efficiency. In general, about 70% of patients are sensitive to the use of glucocorticosteroids, but 20% of those who respond subsequently become resistant to them. Interestingly, some of the patients who did not respond primarily to glucocorticosteroids responded in subsequent attempts, so the trial treatment with glucocorticosteroids should be renewed from time to time (1 time in 1-2 years).

Treatment of patients with Diamond-Blackfang anemia with growth factors-interleukin-3 and erythropoietin, in spite of laboratory prerequisites, was absolutely ineffective. The place of cyclosporine, despite several separate reports of successful treatment, in the therapy of patients with Diamond-Blackkemia anemia is doubtful. Allogeneic bone marrow transplantation can be offered to patients with HLA-genotype sibling if they are not sensitive to glucocorticosteroid treatment.

Patients with glucocorticosteroids that are ineffective or effective at doses that cause unacceptable long-term side effects (osteoporosis, growth disorders, diabetes, cataract, Cushing's syndrome) require competent transfusion and chronic chelation therapy with deferoxamine and / or deferiprone.

Forecast

In the literature, 200 children with anemia of Diamond-Blackfin are cited; 22.5% had spontaneous remission; 41.8% have corticosteroid dependence; in 35.7% - transfusion - dependent remission; 27.6% of children died.