Congenital Neutropenia Syndromes

Congenital neutropenia syndromes are a group of rare disorders present from birth that are characterized by low levels of neutrophils, a type of white blood cell necessary for fighting infections. NIAID supports basic scientific research on the nature and development of neutrophils, which may lead to insights for addressing congenital neutropenia syndromes.

Congenital neutropenia syndromes also may be referred to as congenital agranulocytosis, severe congenital neutropenia, severe infantile genetic neutropenia, infantile genetic agranulocytosis, or Kostmann disease.

Researchers have identified numerous genetic mutations that cause congenital neutropenia syndromes. Generally, mutations that result in congenital neutropenia affect the development, lifespan or function of neutrophils. Congenital neutropenia syndromes are inherited through autosomal recessive, autosomal dominant and X-linked inheritance patterns. The genes linked to these syndromes include the following:

  • HAX1
  • G6PC3
  • GFI1
  • CSF3R
  • X-linked WAS
  • CXCR4
  • VPS45A
  • JAGN1

In some people with congenital neutropenia, however, the disease-causing mutation is unknown.

People with congenital neutropenia experience bacterial infections early in life. These may cause inflammation of the umbilical cord stump, abscesses (or boils) on the skin, oral infections and pneumonia.

Congenital neutropenia also increases one’s risk for developing myelodysplastic syndromes (MDS), blood disorders that are distinguished by low levels of various blood cells. MDS may progress to a type of blood-cell cancer called acute myeloid leukemia.

Bone marrow and blood tests can measure the levels of various white blood cells to test for deficiencies. A person suspected of having congenital neutropenia also may undergo genetic testing.

Standard therapy for congenital neutropenia includes injections of granulocyte colony-stimulating factor (G-CSF), which can help restore immune system function. People on G-CSF therapy may have a lower incidence and severity of infections, improving their quality of life, but effects vary. For some individuals, a bone-marrow transplant may be recommended to replace defective immune cells with healthy ones from a donor.

To learn more about the inheritance pattern of severe congenital neutropenia and find additional information and resources, visit the National Library of Medicine, Genetics Home Reference severe congenital neutropenia site.

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