A fascinating article in the New England Journal of Medicine caught my eye this morning basically saying that a genetic cause has been found for severe congenital neutropenia. The German study found that severe congenital neutropenia can arise from mutations in the gene for glucose-6-phosphatase.
Studies in five patients from two interrelated families of Middle Eastern descent revealed that all were heterozygous for the same mutation in the gene.


The researchers then looked for it in 104 other patients with severe congenital neutropenia with previously unknown genetic origins. Seven of those patients had distinct mutations affecting both alleles. Several different mutations were found.  None of the patients had mutations in other genes known to cause severe congenital neutropenia. The condition is seen in about one in 200,000 births and involves the lack of functioning neutrophils. 


Depending on the gene responsible, other abnormalities may be present as well, including neurological and cardiovascular defects.  In some cases, only neutrophil development is affected.  The gene encodes part of the catalytic region of the glucose-6-phosphatase enzyme, which is involved in multiple glucose metabolism pathways.


Why does this matter?


Well, one of the complications associated with some chemotherapy regimens or drugs is severe neutropenia where the white blood cell count drops drastically below normal and weakens the patient's ability to recover from the treatment because they cannot fight infections. Standard treatment for cancer related symptoms is often to use a growth stimulating factor called G-CSF such as Neulasta (Amgen). Other conditions may also cause a low white blood count such as Lupus, Malaria, Hepatitis viruses, Rheumatoid Arthritis, Aplastic Anemia, Myelodysplastic Syndromes, Parvovirus and others.

Altogether, defects in six separate genes with a variety of functions, are now known to cause neutropenia and explains why some patients suffer from it and others do not.  In addition to the glucose metabolism enzyme encoded by G6PC3, the other mutations are related to mitochondrial function, cytoskeleton integrity, and G-CSF signaling.  One gene encodes a transcription factor of uncertain function, and still another is for the multifunctional neutrophil elastase enzyme. 

What does this all mean?

Well, if you have a condition which is known to sometimes cause low counts and you have the genetic defect, then those patients would most likely benefit from upfront G-CSF treatment to protect against the potential count drop.  This would ensure the patient has a better chance of doing well and also target the costly medication where it is most likely to be needed. 

That's a win-win solution for everyone.