A Non-Fetal Chronic Residual Inflammatory Liver Phenotype After Transient Abnormal Myelopoiesis in Down Syndrome

Transient abnormal myelopoiesis (TAM) in Down syndrome (DS) typically causes acute neonatal liver failure; however, late-onset chronic sequelae remain undercharacterized. We report two patients who, despite achieving hematologic remission, developed a persistent non-fatal inflammatory liver phenotype. Unlike the catastrophic neonatal hemochromatosis-like pathway, these cases exhibited sustained transaminase elevations and fibrotic markers triggered by immune bias rather than blast burden. We propose a two-track model of DS-TAM hepatic sequelae: (i) an acute fatal pathway, and (ii) a chronic residual inflammatory phenotype. These findings expand the clinical spectrum of TAM-associated liver disease, necessitating long-term hepatic surveillance beyond hematologic remission.