Key Takeaways

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.


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