36-hour-old neonate with acute respiratory failure and hypoglycemia

We present the case of a 36-hour-old male, with no personal or family history of interest and no incidents during delivery, who presents with hypoglycemia and acute respiratory failure. The blood count reveals the presence of leukocytosis without anemia or thrombopenia and in the peripheral blood (PB) morphology, 30% immature cells and platelet dysplasia are detected. In view of these findings, the study in PB continues. Using flow cytometry, 44.05% of immature hematopoietic cells (CD45+het, CD34+het, and CD117) are detected expressing antigens suggestive of megakaryoblastic differentiation (CD9+het, CD42b, CD42a, CD61cyt+het, CD41cyt+ het and CD36). The cytogenetic study reveals 47,XY,+21[29]/46,XY[5], and the genetic study of aneuploidies by quantitative fluorescent polymerase chain reaction (QF-PCR) confirms the presence of trisomy 21. Finally, massive sequencing analysis detects a probably pathogenic variant in the GATA1 gene GATA1(NM_002049.4):c.158_159 insTGCAG, p.(Thr54Alafs*85) with a VAF of 56%. All this leads to the diagnosis of transient abnormal myelopoiesis (TAM) associated with down syndrome. TAM is a neonatal transient preleukemic syndrome due to clonal proliferation of megakaryocytic progenitors in the fetal liver. TAM is associated, in all cases, with a mutation in the GATA1 gene, and occurs exclusively in neonates with Down syndrome. With a heterogeneous clinical presentation and incidence rates around 30%, half of them silent, the diagnosis of TAM is important to avoid invasive tests, unnecessary therapeutic actions and establish adequate follow-ups. Up to 20% of cases progress to acute myeloid leukemia associated with Down syndrome (AML-DS) within the first 3 years of life, as it occurred in case #2 presented in this article.