Benign Familial Neutropenia

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Benign Familial Neutropenia

  • Benign – Won’t kill you,
  • Familial – Appearing in individuals by heredity,
  • Neutropenia – Low Neutrophil count

Neutropenia is a blood disorder where an individual has a lower than normal number of neutrophils circulating in their blood. An individual affected by this disease is more susceptible to various types of infections, which can become life-threatening.

Benign Familia Neutropenia is an autosomal dominant genetic disorder which means an individual only needs one copy of the mutant gene to have the disorder. There are three classifications for the disorder based on an Absolute Neutrophil Count. An individual without this disorder will show an ANC above 1500, while someone diagnose with BFN will fit 1 of the 3 classifications:

  • Mild: 1000<1500 ANC – Low risk of infection,
  • Chronic: 500<1000 ANC – At risk for chronic infection,
  • Severe: <500 ANC – Very high risk of infection,

Chromosome location


The location of the gene for BFN is believed to be located at 16q22, being a somewhat rare genetic disease there hasn’t been a big push to research this. An extensive two year testing trial into BFN was completed in 2006 by the Department of Pathology and Department of Medicine at Rhode Island Hospital/Brown Medical School, Rhode Island Laboratory of Cytogenetics, and Quest Diagnostics Nichols Institute in which all patients tested for the disease showed abnormalities at this site.

Characteristics of the Disease


Though there are several types of Neutropenia the symptoms most commonly associated with all types are persistent infections, sore throat, fever, and enhanced swelling around wounds. Unlike individuals with normal neutorphil counts, BFN and the other various types for Neutropenia can be hard to detect due to the fact that individuals with Neutropenia often don’t have pus formations from infections. This is due to the fact that they have a very low number of neutorphils circulating in their blood. Therefore BFN can go undetected in many patients and is usually not found until a severe infection has set in and a WBC is performed. 760px-Neutropenia.jpg

  • WBC test showing RBC’s and Platelets but no WBC

Treatment or Management of the Condition


The disease itself is often not fatal. Like AIDS and Leukemia, having severe BFN isn’t what proves to be fatal but the multitude of infections an individual goes though and the inability of the immune system to suppress and clear the infection is often what leads to the mortality of the disease. There are currently two experimental drugs used to help treat patients with BFN; they are Neupogen and Neulasta and they cost on average around $4,000 per month for the injections. Both drugs are known as GCSF’s (Granulocyte Colony-Stimulating Factor), the difference between the two is that Neulasta (C845H1343N223O243S9 + PEG) has a polyethylene glycol molecule added to one end to increase it’s size so that it circulates in the body for a longer period of time (apprx. 18 – 80 hrs.) compared to Neupogen’s 4 to 6 hrs. These drugs are used to stimulate the bone marrow to increase the number of neutrophils circulating in the blood.

  • Drug Risk! - In some patients Neupogen and Neulasta has caused the spleen to enlarge and in some cases even rupture (This can cause death!). ARDS (Acute respiratory Distress Syndrome) has also been reported in patients as well as bone pain.

Molecular Genetics

In the case study from 2004 – 2006 when the DNA was mapped from a bone marrow biopsy they found that there was a deletion (del16q22) at 16q22. They also found a rare fragile site (fra16q22) that was passed on genetically from parent to child that was expressed phenotypically and cytogenetically. Deletion16q22.jpg Fragile Site16q22.jpg Blown up karyotype.jpg


Genetic Testing

Testing is available for the disease, the test usually performed to check for neutopenia are Blood counts to check for normal levels of WBC and bone marrow biopsy. Both test are accurate in diagnosing whether or not a patient has neutropenia.


Other relevant information

Blood & Bone Marrow.jpg Blood Counts.jpg Blood Study.jpg


References

  • 1) Bernini JC. Diagnosis and management of chronic neutropenia

during childhood. Pediatr Clin North Am 1996;43:773–792.

  • 2) Cutting HO, Lang JE. Familial benign chronic neutropenia.

Blood 1964;61:876–887.

  • 3) Holmes JA, Thompson PW. Expression of fra(10)(q25) in peripheral

blood and bone marrow in familial neutropenia. J Med Genet 1988;25:238–242.

  • 4) Denarier MC. The phagocyte system and disorders of granulopoiesis

and granulocyte function. In: Nathan DG, Orkin SH, Ginsburg D, Look AT, editors. Nathan and Oski’s hematology of infancy and childhood. 6th edition. Philadelphia: Saunders; 2003. p 923–1005.

Lewis Glasser, Aurelia Meloni-Ehrig, Plakyil Joseph, and Jennifer Mendiola; American Journal of Hematology 81:262–270 (2006)

neutropenia in Yemenite Jews. Observations on eleven families. Bull Res Counc Isr Sect E Exp Med 1961;9E:24–28.

  • 11) Shaper AG, Lewis P. Genetic neutropenia in people of African

origin. Lancet 1971;2:1021–1023.

  • 12) Mintz U, Sachs L. Normal granulocyte colony-forming cells in

the bone marrow of Yemenite Jews with genetic neutropenia. Blood 1973;41:745–751.



http://ghr.nlm.nih.gov/condition/pompe-disease Return to Genetic_Disease_Spring 2011 home page.

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