Severe chronic neutropenia (NORD)

Severe chronic neutropenia, or SCN, is a rare blood disorder characterized by decreased neutrophils in the blood lasting from several months to a lifetime and occurring in the absence of systemic disorders like blood cancers and autoimmune diseases or medication use. Neutrophils are the white blood cells that help fight bacterial infections by destroying the invading bacteria. Therefore, a lack of neutrophils results in increased susceptibility to bacterial infections throughout the body. Based on the underlying cause, SCN can be divided into three types - congenital, autoimmune, and idiopathic.

Common signs and symptoms of SCN include recurring fevers; mouth ulcers or sores; gum inflammation which can lead to premature loss of teeth; and recurrent bacterial infections. These may include infections of the skin, referred to as cellulitis; and/or of the mouth, gums, and supportive tissue around the teeth, called stomatitis, gingivitis, and periodontitis, respectively. There may also be infections of the paranasal sinuses, called sinusitis; the throat called pharyngitis; and the lungs, called pneumonia. Sometimes, the infections may even progress to life-threatening complications like sepsis, which is when the body's response to a bloodstream infection causes tissue damage and organ dysfunction.

Although the different SCN subtypes present with similar clinical features, they have varying causes. Congenital SCN, often the most severe subtype, typically presents in infancy or early childhood. It's caused by mutations in the genes which result in the bone marrow producing inadequate or defective neutrophils. The most common mutation involves the ELANE gene, which is inherited in an autosomal dominant pattern. This means that a single defective copy of the gene inherited from either parent is enough to cause the disease. ELANE mutations are also responsible for a rare subtype of congenital neutropenia, called cyclic neutropenia, which is characterized by periodic severe decreases in neutrophil counts. The cyclic pattern remains fixed for each individual and usually recurs every 21 days, with each cycle lasting approximately three to six days. Additionally, congenital SCN also predisposes the person to malignancies of blood cells like myelodysplastic syndrome and certain leukemias, especially acute myeloid leukemia.

Next, autoimmune neutropenia usually affects children between 6 months and 4 years of age, and rarely, adults in the age group of 20 to 30 years. Both the childhood and adult types are mild, but the childhood type usually resolves on its own. Autoimmune neutropenia is caused by the body's immune system producing specific antibodies which attack and destroy the neutrophils circulating in the blood. The neutrophils growing in the bone marrow are usually spared, which provides some protection against infection. Rare forms of autoimmune neutropenia may also be associated with immune-mediated destruction of other blood cells like the red blood cells and platelets.

Finally, in chronic idiopathic neutropenia, the exact cause is unknown, but is thought to be due to some unidentified autoimmune process. The resulting disorder may range anywhere from a self-resolving illness to severe life-threatening complications from infection.