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Genetics of Severe Congenital Neutropenia

written by: R. Elizabeth C. Kitchen•edited by: Emma Lloyd•updated: 7/23/2010

If you or a loved one is suspected to have severe congenital neutropenia an early diagnosis and early treatment is necessary for the best prognosis. Read on to learn more about this disorder, the genetics, and how to recognize it.

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    Severe congential neutropenia, also referred to as Kostmann's syndrome, is a condition in which the neutrophils in the body are severely low. Neutrophils are a white cell responsible for helping the body fight off bacterial infections. Prognosis is good for those who respond to G-CSF therapy, and many patients do. However, if medical intervention is not done within the patient's first year of life, the mortality rate is 70 percent.

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    How Common is this Genetic Disorder?

    About one in 200,000 people are affected by this genetic disorder. This condition affects females and males equally.

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    Genetics of Severe Congential Neutropenia

    Severe Congenital Neutropenia At least five different gene mutations are responsible for causing this genetic disorder. The genes that can cause this disorder when mutated are the genes necessary in helping neutrophils function and mature. Neutrophils, a type of white blood cell produced by the bone marrow, secrete immune molecules that work to consume and destroy foreign invaders. The genes that most often cause this disorder include the ELANE gene and the HAX1 gene when they are mutated. Most patients inherit this disorder in an autosomal dominant pattern, however, in less often cases, this disorder can be inherited in an autosomal recessive pattern. In rare cases, this disorder can be inherited in an X-linked recessive pattern.

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    Symptoms of Severe Congential Neutropenia

    An infection that most often occurs shortly after birth is what typically causes this disorder to be recognized. An infection will most often present with temperature instability, irritability, fever, and at least one localized site of infection. The physical symptoms can include:

    • Oral ulcers
    • Pharyngitis
    • Lymphadenitis and/or lymphadenopathy
    • Cellulitis
    • Omphalitis
    • Lung abscess
    • Liver abscess
    • Peritonitis
    • Septicemia and/or bacteremia (most often caused by staphylococci or streptococci)
    • Bone pain or fractures
    • Neurological symptoms including neuropsychological deficits and epilepsy
    • Gingivitis (may result in losing permanent teeth early)
    • Otitis media and/or sinusitis
    • Pneumonia
    • Bronchitis
    • Boils and/or cutaneous abscess
    • Perianal abscess
    • Enteritis with chronic vomiting and diarrhea
    • Urinary tract infections
    • Splenomegaly

    Children with this disorder have an increased risk for developing leukemia later in their life. Patients with severe congenital neutropenia are also at a high risk for developing potentially life-threatening fungal, bacterial, or mixed infections.

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    Diagnosing this Genetic Disorder

    Diagnosis will begin with the doctor performing a detailed physical examination and taking a detailed medical history. The patient will then have some blood testing done to measure their neutrophil level. Genetic testing can be done to confirm that the patient has this genetic disorder.

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    How is Severe Congential Neutropenia Treated?

    This genetic disorder is most often treated with granulocyte colony-stimulating factor (G-CSF), peripheral blood stem cell transplantation, or bone marrow transplantation.

    G-CSF, also referred to as Neupogen or Filgrastim, is a type of medication known as a biologic response modifier. This medication is used to help prevent neutropenic fevers and infection, and to increase the production of a type of white blood cell known as granulocytes to help prevent low white blood cell counts.

    A bone marrow transplant is a procedure in which health bone marrow stem cells are delivered to a patient to replace any bone marrow that has either been destroyed or is not working properly.

    A peripheral blood stem cell transplantation is a procedure in which stem cells are taken from the patient's own blood and then used to do a bone marrow transplant for the same patient.

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    Tankersley, M. S. MD. (2008). Kostmann Disease. Retrieved on July 20, 2010 from Medscape:

    Genetics Home Reference. (2010). Severe Congenital Neutropenia. Retrieved on July 20, 2010 from Genetics Home Reference:

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