A report of WHIM syndrome (myelokathexis) - clinical features and bone marrow morphology

DOI: 10.5581/1516-8484.20110105 Academia de Ciência e Tecnologia – AC & T, São José do Rio Preto, SP, Brazil Flavio Augusto Naoum Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) syndrome is a very rare form of severe congenital neutropenia with approximately only 40 cases reported until now. The name of this syndrome, WHIM, describes its main features that include, but are not limited to warts, hypogammaglobulinemia, recurrent bacterial Infections and myelokathexis (retention and apoptosis of mature neutrophils in the bone marrow).(1,2) Although recently the molecular basis of this disease was better characterized, the diagnosis of this rare condition remains largely based on clinical features and bone marrow morphology; prompt recognition and initiation of treatment is crucial to avoid morbidity and mortality due to infections. Administration of granulocyte colony-stimulating factor (G-CSF) in this setting reportedly increases the number of neutrophils in circulation and leads to clinical improvement during episodes of bacterial infections.(3,4) Recently a 2-year-old girl was referred to our hematology clinic with a past history of recurrent infections (3 episodes of pneumonia and 5 episodes of urinary tract infection) and persistent low neutrophil counts ranging from 64 to 650 cells/μL since she was 10 months old. Her previous blood counts showed that her hemoglobin concentration and platelet counts were within the normal range. There were no abnormal findings on physical examination. Investigational tests showed hypogammaglobulinemia (gamma globulin at 0.29g/dL) on protein electrophoresis and the examination of the bone marrow aspirate revealed a hypercellular bone marrow with marked granulocytic hyperplasia characterized by an increased number of mature neutrophils with hypersegmented nuclei and cytoplasmic vacuolization. Neutrophils showed nuclear lobes often separated by long strands of chromatin (Figure 1). These typical bone marrow morphologic findings of myelokathexis in association with the clinical picture were consistent with the diagnosis of WHIM syndrome. Treatment with G-CSF (5 μg/kg per day subcutaneously) was initiated after confirmation of diagnosis leading to an increase in neutrophil count to 550 cells/μL after 12 days of therapy, 1300 cells/μL after one month and to 1836 cells/μL after 4 months (Figure 2). No side effects or new episodes of bacterial infection have been observed so far after five months of therapy. The diagnosis of WHIM syndrome was mainly based on the patient's clinical background with recurrent infections and severe chronic neutropenia and on specific laboratorial findings including hypogammaglobulinemia and, more importantly, a bone marrow aspirate showing granulocytic hyperplasia and aberrant