Algorithm for diagnosis and monitoring of mutant GATA1 clones in DS neonates. Suggested algorithm for diagnosis and monitoring of mutant GATA1 clones in DS neonates. Evaluation of a blood smear and CBC can be used as an immediate screening step to identify DS neonates with “classical” TAM who may require early treatment (especially where GATA1 analysis is unavailable or delayed). As a next step, GATA1 mutation analysis by Ss/DHPLC will quickly identify DS neonates with large mutant GATA1 clones. For DS neonates without mutations detected by Ss/DHPLC, NGS is the most reliable way of identifying low-abundance GATA1 mutations, allowing pediatric hematology follow-up to be limited to those at risk of transformation rather than all DS babies with peripheral blood blasts. Monitoring of all DS children with GATA1 mutations until the age of 5 years is recommended. This can be done using serial CBC/smears with GATA1 mutation analysis as indicated (eg, for persistent cytopenias). For the small number of DS babies with blasts >10% who have no detectable GATA1 mutations by NGS, more detailed studies to exclude the presence of rare GATA1 deletions are suggested.