Recurrent Infections in an Infant: Close Monitoring of Sequential Neutrophil Counts Can Identify Cyclic Neutropenia

Abstract

Background: Cyclic neutropenia (CyN) is a rare inherited neutrophil disease characterized by a periodic neutropenia with an absolute neutrophil count (ANC) dropping below 0.5 × 109/L every 3–4 weeks, followed by normalization over the next few days. Clinical Description: A 3-year-old boy presented with recurrent episodes of fever, respiratory tract infections, diarrhea, gingivitis, and oral and cutaneous ulcers from 11 months of age, requiring multiple hospitalizations. He was immunized for age, normal development, with an unremarkable family history. An underlying primary immunodeficiency disorder was suspected in view of recurrent multi-site infections since infancy. Management: The hemogram revealed a normal total leukocyte count with severe, neutropenia, lymphocytosis, normal platelet count and severe anemia . Purified protein derivative test and human immunodeficiency virus test were negative. The chest Xray showed right lower lobe consolidation. Blood culture was sterile. Bone marrow study, immunoglobulin profile, and lymphocyte subtyping were within the normal limits. The child was treated symptomatically with parenteral antibiotics and packed red blood cells transfusion. The ANC increased to 2592/mm3 but, again fell by 27 days after admission. Review of previous blood counts showed a fall and rise of ANC every 3–5 weeks. Clinical exome sequencing revealed a heterozygous mutation in the ELANE gene, a pathogenic variant c. 1A>G (p.Met1), confirming the diagnosis of CyN. The child improved with Granulocyte – colony stimulating factor (G-CSF). Conclusion: Diagnosis of CyN can be challenging as it needs a high index of suspicion and meticulous monitoring of blood counts. If suspected, they should be screened for ELANE mutations.

Keywords

• elane mutation
• primary immunodeficiency
• recurrent oral ulcers