miércoles, 22 de julio de 2015

Congenital Neutropenia Syndromes

Congenital neutropenia syndromes are a group of disorders characterized by low levels of neutrophils— white blood cells necessary for combating infections—from birth. Congenital neutropenia syndromes also may be called

Congenital agranulocytosis
Severe congenital neutropenia
Infantile genetic agranulocytosis
Kostmann's syndrome or disease

Watch neutrophils move towards a Leishmania infection caused by a sandfly bite.
Credit: NIAID

Causes

Researchers have identified a number of genetic mutations that cause congenital neutropenia syndromes. These disorders are inherited in several ways, including autosomal recessive, autosomal dominant, and X-linked.

Genes linked to these syndromes include the following:

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

Generally, mutations that result in congenital neutropenia affect the development, lifespan, or function of neutrophils. In some people however, the disease-causing mutation is unknown.

Signs and Symptoms

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

They also have an increased risk for developing blood disorders called myelodysplastic syndromes (MDS), which are distinguished by low levels of various blood cells. Additionally, MDS may progress to a type of blood cell cancer called acute myeloid leukemia (AML).

Diagnosis

Bone marrow and blood tests can measure the levels of various white blood cells to test for deficiencies. A person suspected of having the disorder may undergo genetic testing for one of the known genetic mutations.

Treatment

Standard therapy includes granulocyte colony-stimulating factor (G-CSF), an immune-cell-growth molecule that can help restore the function of the immune system. People on G-CSF therapy can have a lower incidence and severity of infections, improving their quality of life, but the effects vary between people.

For some individuals, a bone marrow transplantation may be recommended to replace defective immune cells with those of a healthy donor.