IDF understands the challenges when facing a rare diagnosis, such as chronic neutropenia (CN). From locating physicians to providing emotional support, IDF offers programs, services and resources to help you better cope with your diagnosis.
Definition of chronic neutropenia
People with CN have a lower number of neutrophils, a type of white blood cell, for more than 3 months. Neutrophils play an important role in helping the body fight off infection, especially bacterial and fungal infections. The lower a person’s neutrophil count, the greater their risk of infection. CN is both a rare blood disorder and a rare type of primary immunodeficiency (PI).
There are many ways to categorize neutropenia, and you may be diagnosed with neutropenia but not know exactly what type you have. Talk to your doctor about how to get the correct diagnosis.
Neutropenia can be categorized by the following characteristics:
Severity - Based on ANC (Absolute Neutrophil Count) blood test:
- Mild: ANC above 1000 cells per microliter
- Moderate: ANC 500 cells per microliter to 1000 cells per microliter
- Severe: ANC < 500 cells per microliter (0.5 x 109/l)
- Acute: temporary or short-lasting
- Chronic: long-lasting neutropenia symptoms for more than 3 months
- Varying neutrophil counts with a typical cycle length of 21 days
- Congenital: neutropenia that one is born with, runs in families or has a genetic cause
- Acquired: neutropenia that is caused by something else over a period of time
- Idiopathic: neutropenia where the cause is unknown
- Benign ethnic: one of the most common causes of chronic neutropenia in people of African, Middle Eastern and West Indian descent; people with benign ethnic neutropenia are not at increased risk of infection despite their neutropenia
Severe congenital neutropenia is estimated to affect approximately 1-4 people per million population in the United States. CN appears to affect women more than men in its idiopathic and autoimmune forms, with less difference between women and men in congenital forms. Infants, children, and adults can all be affected.
Causes of chronic neutropenia
Some types of CN may be genetically inherited, while others are due to spontaneous genetic mutations that aren’t inherited. These types of neutropenia are called congenital. Some people are simply born with the condition, or the reason may not be known, also known as idiopathic.
Changes or mutations in the ELANE gene are the most common cause of the genetic mutation that causes severe congenital neutropenia and virtually all cases of cyclic neutropenia. Mutations in the CXCR4 gene may also cause chronic neutropenia (and a disease called WHIM syndrome).
Clinical presentation of chronic neutropenia
Chronic neutropenia looks very different depending on how low a person’s level of neutrophils in the blood falls.
Symptoms associated with chronic neutropenia include recurring fevers, mouth sores (ulcers), inflammation of the tissues that surround and support the teeth (periodontitis) and inflammation of the sinuses (sinusitis), throat (pharyngitis) and/or ear (otitis). Due to low levels of neutrophils, people with neutropenia may be more likely to get recurring bacterial infections that, in some people, may result in life-threatening complications.
Chronic neutropenia may be present in the following conditions. If you’re unsure, talk to your doctor about how to get the correct diagnosis.
Diagnosis of chronic neutropenia
Chronic neutropenia can be diagnosed through blood count or genetic testing. Genetic testing is recommended for people with chronic neutropenia. In the last 20 years, newborn screening and other genetic tests have increased the ability of doctors to diagnose many types of PIs, including neutropenias. In turn, researchers and doctors have then been able to discover treatments that target these specific PIs and neutropenias.
Genetic testing for neutropenia may bring you one step closer to an accurate diagnosis and appropriate clinical management, help you make informed choices about your healthcare, learn the risk for your family members, find resources for your condition, and better understand your options for participating in clinical trial research on investigational therapies.
Speak with your doctor or contact a genetic counselor through the patient-initiated testing program about getting a no-cost genetic test from the PATH4WARD program.
Here are some questions to ask your doctor to see if you may benefit from genetic testing:
- Have I had a genetic test?
- If I had genetic testing done before, should I have it done again since there are now tests that look at over 400 genes?
- There are free genetic tests available with a doctor’s referral or through a patient-initiated testing program. Do I qualify for one?
- Is there a chance my diagnosis might change depending on the results of a genetic test?
- Would my treatment change if a genetic test finds that I have a specific type of PI?
- Are there any clinical trials that I might qualify for based on the results of a genetic test?
Treatment for chronic neutropenia
The standard treatment for chronic neutropenia is granulocyte-colony stimulating factors (G-CSF). G-CSF is a manmade version of the hormone that causes the bone marrow to make and release neutrophils, which improves a person’s ability to fight off bacterial and fungal infections. G-CSF is administered through an injection, and side effects can include bone pain and headaches. For people with congenital neutropenia, long-term use of G-CSF may cause pre-leukemia or leukemia.
Investigational therapies for chronic neutropenia
Mavorixafor is an investigational medication that is being studied to see if it can help people with neutropenia by releasing neutrophils from the bone marrow. It works by blocking a receptor known as CXCR4 that is present on immune cells. Mavorixafor has been studied in healthy volunteers as well as people with WHIM syndrome (another PI) and cancer, and all studies showed increases in neutrophil count.
There is currently an open study on Mavorixafor for the treatment of neutropenia. Learn more at: https://clinicaltrials.gov/ct2/show/nct04154488
References and resources
- Severe Chronic Neutropenia. National Organization for Rare Disorders. https://rarediseases.org/rare-diseases/severe-chronic-neutropenia/#:~:te...(SCN)%20is,or%20systemic%20autoimmune%20diseases%20associated. Published 2021. Accessed March 24, 2022.
- ID Your PID. https://www.idyourpid.com/. Published 2021. Accessed March 24, 2022.
- National Neutropenia Network. https://neutropenianet.org/what-is-neutropenia/. Published 2022. Accessed March 24, 2022.
Thank you to X4 Pharmaceuticals, Inc. for their support of this page