a common reason for bringing an infant or child for medical visit is recurrent infections .
this may refer to infections that are too great in number , too severe , or too long lasting ; that are associated with unusual complications ; or that fail to resolve with standard therapy .
only 10% of such cases are due to deficiency in immunity either adaptive or innate .
congenital neutropenia has an estimated frequency of two to three per million in the general population .
elane ( elastase , neutrophil expressed ) gene  related neutropenia includes congenital neutropenia and cyclic neutropenia , both of which are primary hematologic disorders characterized by recurrent fever , skin , and oropharyngeal inflammation ( ie , mouth ulcers , gingivitis , sinusitis , and pharyngitis ) , and cervical adenopathy .
the diagnosis of elane - related neutropenia relies primarily on serial measurements of the absolute neutrophil count ( anc ) and clinical findings .
molecular genetic testing of the elane gene , the only gene known to be associated with elane - related neutropenia , is available on a clinical basis .
a 3-year - old girl was presented to the clinic with the complaint of recurrent fever in mid - september of the year 2009 .
there was no significant birth history . during infancy , she had normal growth and no complaints suggestive of exocrine pancreatic insufficiency . on examination
her stature was normal , there were no abnormality in skin pigmentation . on per abdominal examination
investigations revealed anc of 639 cells / mm , that is , moderate neutropenia but other parameters were in normal range .
she was advised biweekly follow - up for repeat cell count and monitoring for objective evidence of illness due to lack of authoritative past history , ie , history of recurrent fever prior to presentation in the clinic .
she had to present everytime prior to the date of follow - up due to fever with either boils on skin or upper respiratory tract infection symptoms .
it was then decided to put her on antibiotic prophylaxis and self - care advise including dental hygiene were explained to parents .
follow - up visit throughout the period of 3 months showed consistent neutropenia with no cyclical variation in the count .
she neither had any evidence of infection or disease that could result in neutropenia nor was on any drug that could result in the same .
parents of the patient were explained about the possibility of various differential diagnosis that were probable .
the report showed heterozygous mutation in exon2 at nucleotide position t201>a causing a codon change c55>s on polymerase chain reaction amplification followed by direct sequencing of all five exons and the promoter region of the neutrophil elastase ( ela2 ) gene .
patient was started with filgrastim , recombinant methionyl human granulocyte - colony stimulating factor ( g - csf ) ( r - methug - csf ) on the weight - adjusted dosage schedule in february , 2010 .
but in december , 2010 total count rose to 50  10 cells / l .
histopathological examination of bone marrow specimen showed malignant transformation into acute myelogenous leukemia ( aml ) .
most congenital neutropenia is diagnosed because of fever and severe infection in infants and young children . in 1956 , kostmann described congenital neutropenia ( agranulocytosis ) as an autosomal recessive disease occurring in an extended family in northern sweden .
elane ( previously known as ela2 ) is the only gene known to be associated with elane - related neutropenia .
its key physiologic role is in innate host defense , but it can also participate in tissue remodeling and possesses secretagogue actions important to local inflammatory responses .
individuals have fever and recurrent skin and oropharyngeal inflammation , that is , mouth ulcers , gingivitis , sinusitis , pharyngitis , and cervical adenopathy .
diarrhea , pneumonia , and deep abscesses in the liver , lung , and subcutaneous tissues are common .
congenital neutropenia and cyclic neutropenia were initially thought to be distinct disorders ; however , following the discovery of the molecular basis of elane - related neutropenia , individuals with findings intermediate between these two phenotypes are also recognized .
nonetheless , identification of the two phenotypes is helpful for diagnosis , prognosis , and management .
diagnosis requires at least three ancs lower than 500 cells / mm obtained at least 3 months after the birth .
bone marrow aspirate typically shows  maturation arrest  at the promyelocyte or myelocyte stage of neutrophil formation .
the finding of an elane mutation in an individual with neutropenia establishes the diagnosis of elane - related neutropenia .
common side effects of g - csf include bone pain and headache , splenomegaly , and osteoporosis .
individuals with congenital neutropenia ( with or without an elane mutation ) who are treated with g - csf have approximately the same risk of the myelodysplasia syndrome / aml .
the respective cumulative incidences 15 years after starting treatment with g - csf were 36% and 25% ( p=0.96 ) .
the development of aml in our patient was within 10 months after starting g - csf .
this is in contrast to the long 6-year observation period with 9% risk of transformation .
hence , it is prudent to consider the aml as the predisposed malignancy associated with the natural history of these diseases .
hematopoietic stem - cell transplant is the only alternative therapy for individuals with congenital neutropenia who are refractory to high - dose g - csf or who undergo malignant transformation . in our country ,
where infections are very common and the cost of g - csf treatment is high and self - financed , and also when a number of upcoming transplant centers are emerging , it is worthwhile to consider allogenic sibling stem - cell transplant , as one of the treatment modality , especially when there is an human leukocyte antigen ( hla)-matched sibling donor available .
the cost - benefit ratio is much higher with the absence of long - term infectious complications and lesser infrequent hospital admissions . in our centre
, we would start on prophylaxis with g - csf and then search for the hla - matched donor ( especially sibling ) for an allogenic transplant .
 we descibe the case of a girl of indian origin who presented with recurrent infections . 
 the only abnormality detected in the armoury of the immune system was consistent neutropenia . 
 mutation analysis revealed ela2 ( neutrophil elastase ) gene mutation that has been associated with severe congenital neutropenia phenotype . 
 patient was treated with the granulocyte - colony stimulating factor ( g - csf ) as prevention of infectious manifestations along with appropriate measure to curb secondary complications . 
 she showed poor response to the g - csf during stringent surveillance . after being on treatment for 1 year 
 , she developed acute myelogenous leukemia as inherit complication of this disease . 
INTRODUCTION
CASE REPORT
DISCUSSION