Congenital Thrombocytosis, Hepatosplenomegaly, and Rash in a Term Neonate

Objective Transient abnormal myelopoiesis (TAM) is a self-limited clonal myeloproliferative disorder seen almost exclusively in neonates with trisomy 21 and defined by circulating myeloblasts carrying N-terminal truncating GATA1 mutations. Although most cases occur in infants with typical Down syndrome features, TAM can arise in clinically normal newborns with mosaic trisomy 21, creating significant diagnostic uncertainty. Study Design We report a term female neonate who presented with pallor, respiratory distress, hepatosplenomegaly, and a papular, nonblanching rash. Results Laboratory studies showed marked thrombocytosis, leukocytosis, and numerous circulating blasts. Flow cytometry detected a 17% abnormal blast population resembling congenital acute myeloid leukemia, but bone marrow aspirate revealed a myeloproliferative picture without definitive malignancy, favoring TAM. Molecular testing confirmed a truncating GATA1 mutation and mosaic trisomy 21 by SNP array, fluorescence in situ hybridization, and microarray. The infant's condition improved rapidly, with resolution of organomegaly and normalization of blood counts in the first week of life. Conclusion This case underscores the diagnostic challenges of TAM in phenotypically normal infants. Because clinical and laboratory findings can closely mimic congenital leukemia, early evaluation for GATA1 mutations and trisomy 21 is essential to establish the correct diagnosis, guide management, and avoid unnecessary chemotherapy.