Yes. Alpha-thalassemia is inherited in an autosomal recessive pattern, but because four genes are involved, working out the risk for a family is more detailed than for most recessive conditions.
The key question is not only how many genes each parent is missing, but how the missing genes are arranged. Remember that each person carries two chromosome 16 copies, each with two alpha-globin genes. A person with alpha-thalassemia trait is missing two genes, and those two can be arranged in two ways:
• Both missing genes on the same chromosome. One chromosome has no working alpha-globin genes, and the other is normal. This arrangement is called “cis.”
• One missing gene on each chromosome. Each chromosome still has one working gene. This arrangement is called “trans.”
Both arrangements look the same on a blood test, but they carry very different risks for children, because a parent passes on one whole chromosome, not single genes.
When both parents carry the “cis” arrangement, each pregnancy has a 1-in-4 chance of the baby inheriting two empty chromosomes and having hemoglobin Bart’s hydrops fetalis, a 1-in-2 chance of the baby having alpha-thalassemia trait, and a 1-in-4 chance of the baby being unaffected.
When one parent has the “cis” arrangement and the other is a silent carrier or has the “trans” arrangement, each pregnancy has a 1-in-4 chance of hemoglobin H disease. In this situation, hemoglobin Bart’s hydrops fetalis cannot occur, because the second parent always passes on at least one working gene.
When both parents have only single-gene deletions, whether silent carriers or “trans” trait, children cannot have hemoglobin H disease or hydrops from deletions alone.
Only DNA testing can tell which arrangement a person has, which is why couples in whom one partner has small red blood cells should have alpha-globin gene testing, ideally before pregnancy.
Alpha-thalassemia is common in India. Carrier rates range from about 1 to 18 percent in different non-tribal communities and are much higher in some tribal communities. Single-gene deletions are by far the most common type. The “cis” two-gene deletion responsible for hydrops is less common in India than in Southeast Asia, but it does occur, and several different forms of hemoglobin H disease have been reported across at least 13 Indian states.
Alpha-thalassemia can also be inherited alongside beta-thalassemia, and this can change how severe beta-thalassemia is. For couples at risk, options include prenatal diagnosis through chorionic villus sampling or amniocentesis, and preimplantation genetic testing with in vitro fertilization. A genetic counselor can explain what each option means for your family.