Kostmann syndrome D70.0

In 1956, the Swedish pediatrician Rolf Kostmann was the first to describe the disease, which was ultimately named after him, in several siblings from Scandinavian countries (Witkowski 1976).

The German pediatrician Christoph Klein succeeded in identifying the mutated gene in 2007 (Römer 2022).

Kostmann syndrome is one of the severe hereditary neutropenias (Kasper 2015). It is inherited in an autosomal recessive manner (Koletzko 2013). However, spontaneous point mutations in the gene for neutrophil elastase have also been described (Zeidler 2002).

Kostmann syndrome is one of the congenital neutropenias (CN) (Skokowa 2017). The syndrome represents a subtype of CN (Zeidler 2002).

Kostmann syndrome is considered an extremely rare disease. The incidence is 1:300,000 newborns (Römer 2022).

This is a mutation of the HAX-1 gene (Herold 2025). This leads to a standstill in granulopoiesis in the bone marrow at the myelocyte/promyelocyte level (Koletzko 2013).

Kostmann syndrome is a mutation of the genes that encode the granulocyte colony-stimulating factor (G-CSF) receptor and often also neutrophil elastase (Kasper 2015).

Serious, often life-threatening infections occur repeatedly in the first few months of life (Skokowa 2017).

The diagnosis is based on:

• clinical manifestation
• Neutrophil count in the blood
• Bone marrow examination
• Genetic and immunological analyses (Skokowa 2017)

The absolute neutrophil count (ANC) is < 200/ µl (Zeidler 2000).

In addition to lymphocytes and a few erythroblasts, the bone marrow smear also shows larger cells that correspond to precursors of granulopoiesis (Haferlach 2020).

• Life-threatening bacterial infections (Zeidler 2000)
• Life-threatening fungal infections (Reinhardt 2004)
• Acute myeloid leukemia (Koletzko 2013)
• Transition to myeloid neoplasia, Fanconi anemia, dyskeratosis congenita is possible (Spiekermann 2015)

• Antibiotic therapyand cotrimoxazole prophylaxis

Pathogen-specific antibiotics should be used at an early stage, as should cotrimoxazole prophylaxis. However, these measures are not able to keep the children alive in the long term (Reinhardt 2004).

• Granulocyte transfusions

Granulocyte transfusions can be used for severe manifest infections. However, allosensitization must be taken into account here (Reinhardt 2004).

• G-CSF therapy

The disease can be successfully treated causally with G-CSF (human granulocyte growth factor [Pschyrembel]) (Herold 2025). G-CSF is injected subcutaneously on a daily basis (Skokowa 2017).

The initial dose is 3-5 µg/kg bw/day. The dose should then be adjusted accordingly up to a maximum of 120 µg/kg bw/day. The aim of the therapy is to maintain the absolute neutrophil count at > 1,000 /µl (Reinhardt 2004).

• Transplantation

Patients who do not respond to drug therapy can be treated by transplanting haemopoietic stem cells (Zeidler 2000).

Around 90% of affected children can now be treated successfully (Reinhardt 2004).

Without specific therapy, however, Kostmann syndrome is already lethal in the first few years of life (Koletzko 2013).

Regular clinical examinations with annual bone marrow examinations are recommended (Skokowa 2017).

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