Hematopathology Case Study: A Newborn Infant with a High White Blood Cell Count

he affected person is a 1 day outdated child boy born at 39 weeks to a 44 12 months outdated lady. On bodily examination, the newborn had a mildly flattened occiput with thickened nuchal pores and skin, downward slant of palpebral fissures with epichanthal folds and barely low set ears. On imaging, he had a ventricular septal defect. A CBC was carried out which revealed a white depend of 34.2 Ok/uL with a differential that included 37 blasts.

Peripheral Blood Smear 






The peripheral blood confirmed an elevated white depend, many nucleated pink blood cells in addition to a inhabitants of blasts. The cytogenetic evaluation confirmed the suspicion of trisomy 21. Circulate cytometry confirmed that the inhabitants of blasts expressed myeloid in addition to erythroid and megakaryocytic lineage particular antigens. The affected person was discovered to have a GATA1 mutation. Roughly one month after delivery, the affected person’s white depend normalized to 7.2 Ok/uL with solely four circulating blasts counted.


In a affected person with trisomy 21, this presentation is per a prognosis of transient irregular myelopoiesis related to Down syndrome (TAM). TAM happens in 10% of newborns with Down syndrome. Scientific Laboratory Instruments manufacturer Sufferers sometimes current with cytopenias, leukocytosis, a rise in blasts and hepatosplenomegaly. Much less generally, sufferers can have respiratory misery, bleeding, pores and skin rash or jaundice. The blasts are morphologically and immunophenotypically just like these seen in acute myeloid leukemia. They usually have basophilic cytoplasm, coarse basophilic granules and cytoplasmic blebbing, which suggests a megakaryocytic lineage. The immunophenotype typically consists of expression of myeloid markers reminiscent of CD117, CD13 and CD33 plus erythroid and megakaryocytic markers like CD41, CD42b and CD61.1

Along with trisomy 21, mutations in GATA1 are nearly at all times seen within the blast cells of sufferers with TAM. GATA1 is a hematopoetic transcription issue. Bhatnagar, et al. (see diagram under) describe a 3 step mannequin to clarify the evolution of TAM. The preliminary occasion is irregular hematopoesis within the fetal liver attributable to trisomy 21. This causes a rise in megakaryocyte-erythroid progenitors within the hematopoetic stem cell compartment.  The second step is the acquisition of an N-terminal truncating GATA1 mutation earlier than delivery. GATA1 is a regulator of regular megakaryocyte and erythroid differentiation. The truncated mutation causes marked enlargement of megakaryoblastic progenitors.

TAM has a excessive fee of spontaneous remission and sometimes resolves spontaneously in 90% of sufferers over a number of weeks to six months. This coincides with extinction of the GATA1 clone. Nevertheless, in round 10% of those sufferers, myeloid leukemia of Down syndrome (ML-DS) develops inside 5 years of the preliminary presentation. Extra mutations in cohesion element genes and epigenetic regulators happen in these sufferers that lead to clonal enlargement and non-transient leukemia. Kids who develop ML-DS typically have a very good response to chemotherapy and a have a greater prognosis than youngsters with out Down syndrome who develop AML.