Cyclic Neutropenia with mutation in the gene encoding neutrophil elastase (ELA2)

Background and Objective. Cyclic neutropenia is a rare congenital hematopoi etic disease which occurs sporadically or as an autosomal dominantly inheri ted disorder. Recently,the locus for cyclic neutropenia was mapped to chrom osome 19p13.3. Autosomal dominant and sporadic cyclic neutropenia are now a ttributable to mutations of the ELA2 gene encoding neutrophil elastase. Patients/Methods. Based on a case report we review the clinical picture and diagnostic criteria of cyclic neutropenia and report about the recent mole cular biological findings and current treatment options. Results. Serial blood cell counts revealed the characteristic oscillations of the circulating neutrophils with 21-day periodicity from near normal to extremely low levels. The neutrophil nadir lasted 3-5 days. The neutropenia was associated with fever, malaise, painful oral aphthous ulcers and lymph adenopathy. Mutational analysis of the patient's genomic DNA revealed a sin gle basepair transition (nt 4716, G -->A) in intron 4 of ELA2. Since the in itiation of therapy with subcutaneous recombinant human granulocyte-stimula ting colony factor (rHuG-CSF) 24 months ago, the patient has been free of s ymptoms. Conclusions. Despite the typical medical history with onset of the symptoms in early infancy the diagnosis of cyclic neutropenia was not established u ntil the age of 9 years. A common reason for the delayed diagnosis of cycli c neutropenia may be unawareness of the rare but distinctive disorder and t he practice of obtaining screening blood counts without leukocyte different ials. Patients with cyclic neutropenia should be enrolled to the Severe Chr onic Neutropenia International Registry (SCNIR).