Rare Hematology News

Disease Profile

Cyclic neutropenia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

All ages

ageofonset-all.svg

ICD-10

D70

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

rnn-autosomaldominant.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Neutropenia cyclic; Cyclic hematopoiesis

Categories

Blood Diseases; Congenital and Genetic Diseases; Immune System Diseases

Summary

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.[1] 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.[2] Treatment includes prompt treatment of associated infections and and therapies aimed at stimulating the production of neutrophils, such as recombinant human granulocyte-colony stimulating factor (rhG-CSF).[1]

Symptoms

The signs and symptoms of cyclic neutropenia usually appear at birth or shortly after. This condition is characterized by recurrent episodes of neutropenia that recur every 14-35 days (most commonly around 21 days) and last between 3 and 5 days. During times of neutropenia, it may be more difficult for the body to fight bacteria, viruses, and infections. The severity of the resulting infections can vary and are often similar to the severity of the neutropenia itself. Resulting symptoms during periods of neutropenia may include:

  • Recurrent fever
  • Sore throat (pharyngitis)
  • Inflammation of the gums (gingivitis
  • Inflamed and sore mouth (stomatitis)
  • Infections in the skin and in other areas of the body

Additionally, individuals with this condition are at greater risk to develop chronic mouth ulcers. The cycling seems to decrease with age and may disappear by age 30 in some patients. Individuals with cyclic neutropenia only have symptoms during times of neutropenia. At other times when their neutrophil levels are normal, they are not at an increased risk for infection and inflammation.[3][4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Bone pain
0002653
Cyclic neutropenia
0040289
Headache
Headaches
0002315
Sinusitis
Sinus inflammation
0000246
30%-79% of people have these symptoms
Cervical lymphadenopathy
Swollen lymph nodes in the neck
0025289
Fatigue
Tired
Tiredness

[ more ]

0012378
Gingivitis
Inflamed gums
Red and swollen gums

[ more ]

0000230
Oral ulcer
Mouth ulcer
0000155
Periodic fever
0032323
Pharyngitis
0025439
Recurrent skin infections
Skin infections, recurrent
0001581
Respiratory tract infection
Respiratory infection
0011947
Tonsillitis
Inflammation of tonsils
0011110
Tooth abscess
0030757
5%-29% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain

[ more ]

0002027
Atrophy of alveolar ridges
Shrinking of gum ridges
0006308
Cellulitis
Bacterial infection of skin
Skin infection

[ more ]

0100658
Decreased eosinophil count
0031891
Lymphopenia
Decreased blood lymphocyte number
Low lymphocyte number

[ more ]

0001888
Opportunistic infection
0031690
Otitis media
Middle ear infection
0000388
Perianal abscess
0009789
Periodontitis
0000704
Premature loss of permanent teeth
Early loss of adult teeth
Early loss of permanent teeth
Premature loss of adult teeth

[ more ]

0006357
Thrombocytopenia
Low platelet count
0001873
1%-4% of people have these symptoms
Bacteremia
0031864
Enterocolitis
0004387
Peritonitis
0002586
Sepsis
Infection in blood stream
0100806
Severe infection
0032169
Percent of people who have these symptoms is not available through HPO
Abnormality of the mouth
Abnormal mouth
0000153
Autosomal dominant inheritance
0000006
Fever
0001945
Neutropenia
Low blood neutrophil count
Low neutrophil count

[ more ]

0001875

Diagnosis

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.[2][3]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment for cyclic neutropenia includes taking antibiotic medicines for fevers and infections. People with abdominal pain need to be carefully evaluated for the potentially serious complications of peritonitis and bacteremia.[2]

    Treatment with granulocyte colony-stimulating factor (G-CSF), also called Neupogen, is effective in raising blood neutrophil counts in cyclic neutropenia. G-CSF treatment reduces the symptoms and problems of infections in almost all people. Treatment is may be started 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.[2]

    Common side effects of G-CSF include bone pain and headache, enlarged spleen, and osteoporosis. Less common side effects include vasculitis, rashes, joint pain, and kidney disease (glomerulonephritis).[2]

    For people with a well-matched donor, a bone marrow transplant may be the preferred treatment option. HSCT is the only alternative therapy for individuals with congenital neutropenia who do not respond to G-CSF or who undergo malignant transformation to cancer.[2]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Cyclic neutropenia. Click on the link to view a sample search on this topic.

          References

          1. Boxer, LA. Neutropenia, Cyclic. National Organization for Rare Disorders (NORD). 2015; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/663/viewAbstract.
          2. Dale DC. ELANE-Related Neutropenia. GeneRevews. July 2011; https://www.ncbi.nlm.nih.gov/books/NBK1533/.
          3. Coates TD. Cyclic Neutropenia. UpToDate. May 09, 2016; https://www.uptodate.com/contents/cyclic-neutropenia.
          4. Cyclic neutropenia. Genetics Home Reference (GHR). January 2012; https://ghr.nlm.nih.gov/condition/cyclic-neutropenia. Accessed 3/17/2014.

          Rare Hematology News