Alpha-thalassemia is a genetic condition in which the body makes too little of a protein called alpha-globin. Alpha-globin is one of the two building blocks of hemoglobin, the molecule inside red blood cells that carries oxygen around the body. When alpha-globin is in short supply, red blood cells come out smaller, paler, and more fragile than usual, and this can lead to anemia, a shortage of healthy red blood cells.

Hemoglobin in adults is made of two alpha-globin chains paired with two beta-globin chains. Unlike beta-globin, which is made from a single gene, alpha-globin is made from four gene copies. Every person normally has two alpha-globin genes, called HBA1 and HBA2, sitting side by side on each copy of chromosome 16. Since we inherit one chromosome 16 from each parent, that adds up to four working alpha-globin genes in total.

In most people with alpha-thalassemia, one or more of these four genes is missing, usually because a small piece of DNA has been deleted. Less often, a gene is present but carries a harmful change that stops it working properly. The more genes that are missing or not working, the less alpha-globin the body can make, and the more severe the condition:

• One gene affected: a silent carrier, usually with no signs at all
• Two genes affected: alpha-thalassemia trait, usually a very mild anemia with no symptoms
• Three genes affected: hemoglobin H disease, a lifelong anemia that ranges from mild to severe
• All four genes affected: hemoglobin Bart’s hydrops fetalis, a severe condition that begins before birth

A useful way to picture this is a factory with four machines making the same part. Losing one machine barely changes output. Losing two slows things a little. Losing three causes real shortages. Losing all four stops production altogether.

When alpha-globin runs short, the leftover partner chains have nothing to pair with. They clump together into abnormal forms of hemoglobin, called hemoglobin H in children and adults and hemoglobin Bart’s before birth. These forms do not deliver oxygen well and make red blood cells break down early.

Alpha-thalassemia is not caused by anything a parent did during pregnancy, and it cannot be caught from another person. It comes entirely from the alpha-globin genes a child inherits.