Kostmann Syndrome: Symptoms, Causes, Treatment

What are the symptoms of Kostmann syndrome?

Kostmann syndrome, also known as severe congenital neutropenia, is characterized by a dangerously low level of neutrophils, leading to recurrent bacterial infections from an early age. The main symptoms include:

1. Frequent infections: This can include:

• Pneumonia
• Ear infections (otitis media)
• Skin infections (cellulitis, abscesses)
• Gum infections (gingivitis)

1. Poor wound healing: Cuts and injuries may heal more slowly due to the lack of neutrophils.
2. Fever and fatigue: Recurrent infections can lead to chronic fever and general malaise.
3. Mouth ulcers and gum disease: Painful sores and inflammation of the gums (gingivitis) are common due to infections in the mouth.
4. Bone marrow abnormalities: A bone marrow biopsy may show an absence of mature neutrophils, though other blood cells may appear normal.

Without treatment, individuals with Kostmann syndrome are at risk of life-threatening infections. Early diagnosis and management, often with granulocyte colony-stimulating factor (G-CSF), can help boost neutrophil production and reduce infection risks .

What are the causes of Kostmann syndrome?

Kostmann syndrome, also known as severe congenital neutropenia (SCN), is caused by genetic mutations that affect the development and survival of neutrophils, a critical type of white blood cell. One common cause is a mutation in the HAX1 gene, which plays a role in cell survival, particularly in the bone marrow where neutrophils are produced. This mutation leads to increased cell death of neutrophil precursors. Another cause is mutations in the ELANE gene, which encodes neutrophil elastase, a protein essential for the function and maturation of neutrophils. Mutations in ELANE interfere with neutrophil development and contribute to the low neutrophil count seen in the disorder. Additionally, other less frequent genetic mutations, such as those in the G6PC3, GFI1, and CSF3R genes, can also cause related forms of congenital neutropenia. Kostmann syndrome is inherited in an autosomal recessive pattern, meaning a child must inherit two defective copies of the gene (one from each parent) to manifest the condition.

Treatment typically involves granulocyte colony-stimulating factor (G-CSF) to encourage neutrophil production and, in severe cases, bone marrow transplantation.

What is the treatment for Kostmann syndrome?

The primary treatment for Kostmann syndrome (severe congenital neutropenia) focuses on increasing neutrophil production to prevent life-threatening infections. The main treatments include:

1. Granulocyte Colony-Stimulating Factor (G-CSF): This is the first-line treatment for Kostmann syndrome. G-CSF is a medication that stimulates the bone marrow to produce more neutrophils. It is usually administered via injections, and most patients respond well to this treatment, maintaining safer neutrophil levels. However, regular monitoring is needed, as some patients may develop resistance or complications over time.
2. Antibiotics: Since people with Kostmann syndrome are highly susceptible to bacterial infections, antibiotics are often used preventively (prophylactically) or to treat infections as they occur.
3. Bone Marrow Transplant: For patients who do not respond adequately to G-CSF or develop complications such as leukemia, a bone marrow (or hematopoietic stem cell) transplant may be considered. This procedure can provide a long-term cure by replacing the defective bone marrow with healthy marrow from a compatible donor.
4. Gene Therapy (experimental): In the future, gene therapy may offer a potential treatment for Kostmann syndrome by correcting the genetic mutation responsible for neutropenia, but this is still in the experimental phase.

Regular monitoring by a healthcare team is crucial for managing the disease, and adjustments to treatment may be needed depending on the patient’s response.