What are the other Names for this Condition? (Also known as/Synonyms)

• Neutropenia, cyclic
• Cyclic Hematopoiesis

What is Cyclic Neutropenia? (Definition/Background Information)

• Cyclic Neutropenia is a rare blood disorder characterized by recurrent episodes of abnormally low levels of neutrophils (a type of white blood cell) in the body
• Neutrophils are instrumental in fighting-off infection by surrounding and destroying bacteria that enter the body
• Symptoms of Cyclic Neutropenia may include fever, a general feeling of ill health, and/or sores (ulcers) of the mucous membranes of the mouth
• Individuals with low levels of neutrophils (neutropenia) are highly susceptible to recurrent infections
• Cyclic Neutropenia may be inherited or acquired. Some cases are present at birth and appear to occur randomly for no apparent reason (sporadic)
• Inherited cases appear to be transmitted in an autosomal dominant fashion and are caused by mutations in the ELANE gene
• Treatment includes prompt treatment of associated infections and therapies aimed at stimulating the production of neutrophils, such as recombinant human granulocyte-colony stimulating factor (rhG-CSF)

(Source: Cyclic Neutropenia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Cyclic Neutropenia? (Age and Sex Distribution)

• Cyclic Neutropenia is a rare congenital disorder. The presentation of symptoms may occur at or following the birth of the child
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Cyclic Neutropenia? (Predisposing Factors)

• A positive family history may be an important risk factor, since Cyclic Neutropenia is an inherited condition
• Currently, no other risk factors have been clearly identified for this disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Cyclic Neutropenia? (Etiology)

• Cyclic Neutropenia may be inherited or acquired. Some cases are present at birth and appear to occur randomly for no apparent reason (sporadic)
• Inherited cases appear to be transmitted in an autosomal dominant fashion and are caused by mutations in the ELANE gene
• In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family

(Source: Cyclic Neutropenia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Cyclic Neutropenia?

The signs and symptoms of Cyclic Neutropenia may include:

• Abnormality of the mouth
• Cyclic Neutropenia
• Fever

Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases:

• Anemia
• Fatigue                   
• Neutropenia
• Oral ulcer
• Overlapping toe
• Recurrent skin infections
• Sepsis

Frequently present symptoms in 30-79% of the cases: Periodontitis

Occasionally present symptoms in 5-29% of the cases:

• Abnormality of eosinophils 
• Carious teeth 
• Lymphadenopathy
• Recurrent aphthous stomatitis                   
• Recurrent respiratory infections 
• Thrombocytopenia

(Source: Cyclic Neutropenia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Cyclic Neutropenia Diagnosed?

• The diagnosis of Cyclic Neutropenia may be suspected based on signs and symptoms including regular, cyclic fluctuations in the level of neutrophils in the blood
• The diagnosis of Cyclic Neutropenia is often confirmed by blood work including measurement of an absolute neutrophil count that is less than 200/microL during periods of neutropenia on multiple days within at least 3 regularly spaced cycles
• Genetic testing can additionally be helpful to confirm the diagnosis

(Source: Cyclic Neutropenia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Cyclic Neutropenia?

The complications of Cyclic Neutropenia may include:

• Presence of recurrent infections, which may be severe and life-threatening
• Tooth abnormalities

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Cyclic Neutropenia Treated?

• Conventional management of Cyclic Neutropenia includes prompt treatment of fevers and infections with antibiotics
• Individuals with abdominal pain require careful evaluation for the potentially lethal complications of peritonitis and bacteremia
• Treatment with granulocyte colony-stimulating factor (G-CSF), also called Neupogen, is effective in elevating blood neutrophil counts in cyclic neutropenia. G-CSF treatment ameliorates the symptoms and problems of infections in almost all affected individuals
• In Cyclic Neutropenia, G-CSF shortens the periods of neutropenia as well as the length of the neutropenic cycle
• Treatment is known to be effective at least as early as age six months to one year
• Studies indicate that treatment is effective with no adverse effects on growth, development, or pregnancy outcome with follow-up to age 18 years
• Common side effects of G-CSF include bone pain and headache, splenomegaly, and osteoporosis
• Vasculitis, rashes, arthralgias, and glomerulonephritis have been infrequently reported
• For affected individuals with a well-matched donor, hematopoietic stem cell transplantation (HSCT) may be the preferred treatment option
• HSCT is the only alternative therapy for individuals with Congenital Neutropenia who are refractory to high-dose G-CSF or who undergo malignant transformation

(Source: Cyclic Neutropenia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Cyclic Neutropenia be Prevented?

Currently, the inherited cases of Cyclic Neutropenia may not be preventable. In such cases, the following may be noted:

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Cyclic Neutropenia? (Outcomes/Resolutions)

• The prognosis of Cyclic Neutropenia is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Cyclic Neutropenia:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/