✅ Alpha-thalassemia is an autosomal recessive inherited disorder of red blood cells. It can rarely occur as an acquired defect in disorders associated with ineffective erythropoiesis, especially myelodysplastic syndrome (MDS).
✅ Acquired α-thalassemia myelodysplastic syndrome (ATMDS) is HbH disease (α-thalassemia, AT) in association with a chronic myeloid disorder (usually MDS).
✅ ATMDS is caused by reduced synthesis of α-globin chains related to a dramatic downregulation of α-globin gene expression by inactivating mutations of the ATRX gene, which encodes the chromatin remodeling factor ATRX.
✅ Somatic mutations in the ATRX gene occur in ~ 0.8% of patients with MDS.
✅ > 5:1 male-female ratio, median age at diagnosis of 68 years.
✅ In contrast to most patients with MDS who have macrocytic or normocytic anemia, patients with α-thalassemia myelodysplastic syndrome (ATMDS) typically present with severe microcytosis and hypochromia.
✅ Diagnosis is suspected in a patient with MDS and microcytosis.
✅ Diagnosis is confirmed by demonstrating excess α-chains form homotetramers (HbH, β4).
✅ About 25% of patients with AT-MDS will progress to AML; this risk of progression appears to be similar to that of the general MDS patient population.