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What
Kostmann's agranulocytosis is a condition that causes low levels of white blood cells at birth. The low level of white blood cells is due mainly to the extremely low levels of a specific type of white blood cell called neutrophils. Neutrophils are part of a group of white blood cells that are one of the body's first lines of defense against many bacterial infections. Because neutrophils play a role in the defense of the body against infection, children with this condition are at higher risk for infection due to the reduced levels.
Who
The incidence of congenital neutropenia is estimated to be 1 or 2 cases per one million people internationally.
Signs and Symptoms
Children with Kostmann's agranulocytosis have extremely low levels of neutrophils on blood counts and can get a variety of frequent bacterial infections. In early infancy, they can present with unstable temperature and fevers, as well as irritability. The most commonly seen bacterial infections in Kostmann's agranulocytosis are skin abscesses and boils, ear infections, sinusitis, pharyngitis, lung infections, gingivitis and oral ulcers. In addition to effects on the immune system, some children with Kostmann's agranulocytosis may have medical conditions involving the brain, such as developmental delay and seizures. About 20% of children with Kostmann's agranulocytosis go on to develop Acute Myeloid leukemia (AML).
Possible Causes
The cause of the signs and symptoms of Kostmann's agranulocytosis is due to the low levels of neutrophils. The cause of the low levels of neutrophils is likely genetic. Kostmann's agranulocytosis is an inherited autosomal recessive condition. Therefore, it takes two abnormal copies of the gene (one from each parent) to develop the disease. In this case, both parents are carriers of this disease, which means that they each have one normal copy of this gene and one abnormal copy. Although the parents do not have any symptoms of disease, there is a 1 in 4 (25%) chance with every pregnancy that they will have a child with Kostmann's. Some individuals with Kostmann's agranulocytosis have been shown to have an inherited change in both copies of a gene called HAX1, which normally protects neutrophils from dying.
Diagnosis
If a child is having reoccurring infections, the physician may first order some blood work called a complete blood count (CBC) to determine the levels of the various blood cell types in the child's body. To specifically determine the levels of neutrophils in the body, an absolute neutrophil count (ANC) may be ordered. If the levels of neutrophils are proven to be low, the blood work may be repeated to confirm the levels or a sample of bone marrow may be taken to further assess the level of neutrophils. Bone marrow is a liquid like substance in the center of bone that is the birthplace for blood cells. Determining the levels of various blood cell types at that location can be helpful in determining when the problem occurs in the ongoing development of the blood cells.. Patients with Kostmann's agranulocytosis will have low levels of neutrophils in their bone marrow. Sometimes multiple repeated blood tests are needed to exclude other, more common causes of low neutrophil counts, such as a disease called cyclic neutropenia. In some individuals, a blood test looking for HAX1 gene mutation may also be done.
Treatment
The treatment for Kostmann's agranulocytosis may vary depending on the specific conditions related to the child. The child may be given a substance called granulocyte-colony stimulating factor (G-CSF). This substance is normally produced by the body and stimulates the immature blood cells to grow into neutrophils. This treatment will be life long. The child will also need life long monitoring of his/her CBC to make sure the levels of neutrophils are being properly maintained as well as prompt treatment of all infections. Since these children are susceptible to bacterial infections, they benefit greatly from vaccinations against common bacterial organisms. For children who are not responsive to therapy with G-CSF or those who develop leukemia, bone marrow transplantation is an option.
Prognosis
The prognosis of a child diagnosed with Kostmann's agranulocytosis will depend largely on how well he/she responds to treatment and how many severe infections the child contracts. Regardless, the child will need life long treatment and close monitoring. Children with Kostmann's agranulocytosis are at an increased risk for developing acute myeloid leukemia. This is thought to be due to another mutation that is acquired later in life. This mutation is in a gene that makes granulocyte colony-stimulating factor receptor (CSF3R).
Connect with other parents
In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, Please fill out this brief form.
Connect with other parents
In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.Weblinks
Klein, C. et al. (2007). HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nature Genet. 39: 86-92.
Schaffer, A., Klein C. (2007). Genetic heterogeneity in severe congenital neutropenia: how many aberrant pathways can kill a neutrophil? Curr Opin Allergy Clin Immunol. 7(6): 481-94, Dec 2007.