CPT® Code 81259

HBA1/HBA2 (alpha globin 1 and alpha globin 2) (eg, alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis; full gene sequence

Molecular genetic testing is a critical procedure used to identify specific mutations in the HBA1 and HBA2 genes, which are responsible for encoding the alpha globin chains of hemoglobin. These genes are located on chromosome 16 within the alpha globin locus and play a significant role in various hemoglobin disorders. Among these disorders, alpha thalassemia is the most prevalent globally, resulting from the absence or reduced production of alpha globin chains due to deletions in the alpha A genes, which include both HBA1 and HBA2. There are several known variants of alpha thalassemia, including SEA, THAI, FIL, MED, and alpha20.5, which involve deletions of both HBA1 and HBA2 from the same chromosome. Other variants, such as alpha3.7 and alpha4.2, result in the deletion of a single alpha gene, while the Constant Spring (HbCS) variant is characterized by a mutation in the termination codons of HBA2, leading to an elongated protein structure by 31 amino acids. The inheritance pattern of these disorders is autosomal recessive, meaning that individuals must inherit mutations in both copies of the gene from their parents to develop hemoglobin disorders. Those who inherit a mutation from only one parent become carriers of the disease. Clinically significant forms of alpha thalassemia include Hb Bart, which can lead to hydrops fetalis syndrome due to the loss of all four alpha globin genes, resulting in severe complications such as fetal and perinatal death, edema, and severe anemia. Another form, Hemoglobin H (HbH) disease, occurs with the loss of three alpha genes and presents with moderate anemia and splenomegaly. Carrier states may exhibit mild anemia and can often be misdiagnosed as iron deficiency anemia. Silent carriers, who lose only one alpha gene, are typically asymptomatic or may show very mild symptoms. Molecular genetic testing is particularly indicated for individuals exhibiting symptoms of hemoglobin disorders, women with a history of fetal loss associated with hydrops fetalis syndrome, or those with a family history of these conditions.