Alpha-Thalassemia

Alpha-thalassemia is an inherited disorder that affects the blood's ability to carry oxygen. There are two types of alpha-thalassemia, hemoglobin H (HbH) disease and hemoglobin Bart hydrops fetalis (Hb Bart) syndrome. The milder type, HbH disease, causes moderate anemia (too few red blood cells), weakness, fatigue, spleen and liver problems, as well as characteristic bone changes in the forehead or upper jaw. Symptoms typically appear in childhood and survival is into adulthood. Some individuals with HbH disease may not require any special medical treatment and some may require regular blood transfusions. The more severe type, Hb Bart syndrome, is generally diagnosed during pregnancy because it causes fluid to build up in the body before birth. It also causes severe anemia and problems with the liver and heart. Babies with Hb Bart syndrome are stillborn or die soon after birth. Alpha-thalassemia is caused by pathogenic variants on the HBA1 and HBA2 genes.

Alpha-thalassemia is inherited in an autosomal recessive manner. Normally two alpha hemoglobin genes are inherited from each parent, one HBA1 gene and one HBA2 gene, for a total of four alpha hemoglobin genes. If a parent is missing one or two of these genes, then their children are at risk of having alpha-thalassemia. HbH disease results from inheriting only one good alpha hemoglobin gene. Hb Bart syndrome results from inheriting no alpha hemoglobin genes.

Carriers of alpha-thalassemia may have mild anemia or no medical issues. The risk to have a child affected with alpha-thalassemia is increased; however, the severity varies based on the type of pathogenic variants present. Testing of reproductive partners, with consideration to their ethnicity, is recommended for carriers of alpha-thalassemia.

Alpha-thalassemia is most frequent in Southeast Asian populations, where the incidence of HbH disease is between 4 and 20 per 1000 births, and the incidence of Hb Bart syndrome is between 0.5 and 5 per 1000 births. Frequency is also increased in Mediterranean countries, the Middle East, India, Central Asia and North Africa.

Genetics Home Reference: Alpha-thalassemia (http://ghr.nlm.nih.gov/)
Genetic Alliance: Alpha-thalassemia (http://www.diseaseinfosearch.org/)

OMIM [Alpha-thalassemia: 604131] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Alpha-thalassemia (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

• Full gene sequencing
• Copy number analysis: HBA1 and HBA2