What are the signs of alpha-thalassemia, and how is it diagnosed?

[Anonymous]

What are the signs of alpha-thalassemia, and how is it diagnosed?

[Genetic Counselor]

Signs of alpha-thalassemia depend on how many of the four alpha-globin genes are affected.

• Silent carrier and alpha-thalassemia trait These individuals are healthy. Blood counts may show slightly small, pale red blood cells, sometimes with a mild anemia. Most people only find out through routine blood tests, pregnancy screening, or when a relative is diagnosed.
• Hemoglobin H disease Symptoms vary a great deal. Some individuals have a mild anemia and live normally. Others have tiredness, pale skin, mild yellowing of the skin and eyes (jaundice), an enlarged spleen, and gallstones. A key feature is sudden drops in hemoglobin, called hemolytic crises, often triggered by fever, infection, pregnancy, or certain medicines. Forms caused by gene changes rather than deletions tend to be more severe, and some children need regular blood transfusions.
• Hemoglobin Bart’s hydrops fetalis This is usually picked up on pregnancy ultrasound. The baby develops severe anemia before birth, leading to fluid build-up around the body, an enlarged heart, liver, and spleen, and a thickened placenta. Without treatment during pregnancy, it is usually fatal before or shortly after birth.

Diagnosis usually begins with a complete blood count, which shows small, pale red blood cells. The next step is a hemoglobin analysis test, such as high-performance liquid chromatography or electrophoresis. This test is very good at finding beta-thalassemia trait, but it has an important limitation: in alpha-thalassemia trait, the results are usually normal. This means a person can be told their thalassemia screen is “normal” and still carry alpha-thalassemia. This matters in India, where routine screening is designed mainly around beta-thalassemia.

In hemoglobin H disease, the hemoglobin analysis shows hemoglobin H, and a special stain of the blood shows characteristic clumps inside red blood cells. In newborns, hemoglobin Bart’s can be measured at birth.
Confirmation comes from DNA testing of the HBA1 and HBA2 genes. This usually starts by checking for common deletions, then gene sequencing and deletion analysis if needed. When red blood cells are small and pale but iron levels and hemoglobin analysis are normal, DNA testing for alpha-thalassemia is the right next step. It also avoids giving iron tablets to people who do not need them, as extra iron can be harmful.

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