JM case reports session

Background: Somatic gain-of-function (GOF) mutations in STAT5B, particularly N642H, are well-established in hematologic malignancies, such as leukemia and lymphoma, often presenting with significant eosinophilia.A distinct phenotype involving nonmalignant manifestations has been rarely reported.This phenotype is characterized by early-onset hypereosinophilia, urticaria, dermatitis, and diarrhea.Case Presentation: We report the case of a 9-year-old boy with a history of early infancy hypereosinophilia, severe asthma, atopic dermatitis, and food allergies.He later developed lymphadenopathy, hepatosplenomegaly, subcutaneous nodules, orbital pseudotumor and failure to thrive, with growth parameters consistently below the 3rd percentile.His short stature was investigated and was attributed to growth hormone deficiency.Growth hormone replacement therapy failed to improve his height.The patient is the second child of non-consanguineous parents, with two healthy siblings and a family history of stomach cancer.Laboratory findings revealed, leukocytosis (19,000-68,000/ L), lymphocytosis (12,600-22,700/L) with eosinophilia (1500-38,000/L), serum IgE levels exceeding 5000 IU/ml.Lymphocyte immunophenotyping revealed lymphocytosis with dominant CD3CD8 cells.Esophagogastroduodenoscopy showed significant eosinophilic infiltration throughout the GI system.The whole exome sequencing identified a heterozygous STAT5B N642H missense mutation.He was managed initially with prednisone 4 mg/kg/day tapered based on clinical response then shifted to IL-5 antagonist monoclonal antibody Mepolizumab 100 mcg monthly.The patient showed clinical improvement, with resolution of lymphadenopathy, hepatosplenomegaly,orbital pseudotumor, subcutaneous nodules, and a marked reduction in hospitalizations and eosinophil count (200-600/L).Discussion: This case expands the clinical phenotype of STAT5B N642H heterozygous mutation to include hepatosplenomegaly, lymphadenopathy, subcutaneous nodules, orbital pseudotumor, and growth hormone deficiency.We consider the mutation a somatic gain of function based on the previous reported pathologies related to STAT5B N642H mutation.However, the growth hormone deficiency and the failure to respond to growth hormone replacement urge for further study to identify the impact of STAT5B N642H mutation on the protein function in our patient.Conclusion: This report highlights the diverse phenotypic presentations associated with the STAT5B N642H mutation.It also showed for the first time that Mepolizumab controls disease activity.Expanding knowledge about STAT5B mutations will contribute to improved recognition, management, and potentially targeted therapies for affected patients.