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Kostmann syndrome: causes, symptoms, diagnosis, treatment
Medical expert of the article
Last reviewed: 04.07.2025
Kostmann syndrome (childhood genetically determined agranulocytosis) is the most severe form of hereditary neutropenia.
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Causes of Kostmann syndrome
The inheritance pattern is autosomal recessive, there may be sporadic cases and a dominant inheritance pattern. In some patients, mainly in sporadic forms, a mutation of the gene encoding the formation of neutrophil elastase (ELA-2 gene) has been identified. The level of the genetic defect has not yet been found. Some patients with Kostmann syndrome (13-27%) have a point mutation of the granulocyte colony-stimulating factor receptor gene. These patients belong to the high-risk group for the development of myelodysplastic syndrome and acute myeloid leukemia.
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Symptoms of Kostmann syndrome
Kostmann syndrome - the disease debuts in the first months of life or in the neonatal period in the form of severe recurrent bacterial infections: stomatitis, chronic gingivitis, repeated pneumonia, including destructive. Deep agranulocytosis is typical (<0.3x10 9 /l neutrophils). The myelogram is characteristic: only dividing neutrophilic cells, promyelocytes and/or myelocytes are preserved, the number of eosinophils and monocytes is increased. Atypical nuclei, large azurophilic granules and vacuoles in the cytoplasm are found in promyelocytes. Without special treatment, patients used to die by 2-3 years.
Treatment of Kostmann's syndrome
The main method of treatment for Kostmann syndrome is recombinant granulocyte colony-stimulating factor (filgrastim and lenograstim) in a therapeutic dose of 6-100 mcg/kg per day, the drug is administered subcutaneously. The maintenance dose is selected individually to maintain the absolute neutrophil count above 1000/mm 3. It is used for life, and is well tolerated. During periods of exacerbation of infections, broad-spectrum antibiotics and antifungal drugs are used. In particularly severe cases, transfusions of donor granulocytes are indicated. Given the high risk of developing leukemia, patients should be under medical supervision with dynamic assessment of the hemogram. In case of resistance to treatment with granulocyte colony-stimulating factor or the appearance of a mutation in the granulocyte colony-stimulating factor receptor gene, allogeneic bone marrow transplantation is indicated.