Cyclic neutropenia – ELANE gene 

Cyclic neutropenia, also called cyclic hematopoiesis or cyclic leukopenia, is an alteration that causes frequent infections and other health problems in affected individuals. People with this condition have recurrent episodes of neutropenia (neutrophil deficiency) that become apparent right after birth or shortly thereafter. In cases with a greater degree of involvement, neutropenia is repeated every 21 days, and lasts 3 to 5 days.

Neutropenia makes it more difficult for the body to fight pathogens such as bacteria and viruses, so people with this disorder often develop periodic infections of the sinuses, respiratory tract and skin. In addition, these people frequently develop mouth and colon ulcers, gingivitis, pharyngitis, recurrent fever, or abdominal pain, which manifest only during episodes of neutropenia. When neutrophil concentrations are normal, they don’t have increased risk of infections.

This process is due to ELANE gene mutations (elastase, neutrophil expressed), located on the short arm of chromosome 19 (19p13.3), which encodes the neutrophil elastase protein. Neutrophils have an important participation in inflammatory processes and in the defense against infections. When the body begins an immune response to fight an infection, neutrophils release elastase, which modifies the function of certain cells and proteins to help fight the infection.

More than 15 mutations in the ELANE gene causing cyclic neutropenia have been identified. Mutations in the gene change the amino acids in the neutrophil elastase. It is believed that these mutations give rise to an abnormal protein that retains part of its function. However, neutrophils that produce abnormal elastase appear to have a shorter lifespan than normal. When the affected neutrophils die soon, periods with a shortage occur until the body replenishes them.

In addition, more than 70 mutations in the ELANE gene have been identified in individuals with severe congenital neutropenia, characterized by the existence of neutropenia since childhood. Most of these mutations alter the structure of neutrophil elastase, causing it to fold in an incorrect three-dimensional shape and accumulate. This accumulation causes damage and kills these cells. A neutrophil deficiency causes recurrent infections, episodes of inflammation and other immune system problems in people with severe congenital neutropenia.           

Cyclic neutropenia is inherited with an autosomal dominant pattern, which means that one copy of the altered gene in each cell is sufficient to cause the disease. In most cases an affected person inherits the mutation of an affected parent. Other cases are the result of new mutations in the gene and occur in people with no history of the disease in their family.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with cyclic neutropenia, by means of the complete PCR amplification of the exons of the ELANE gene, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leukocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).