CPT® Code 81257

HBA1/HBA2 (alpha globin 1 and alpha globin 2) (eg, alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis; common deletions or variant (eg, Southeast Asian, Thai, Filipino, Mediterranean, alpha3.7, alpha4.2, alpha20.5, Constant Spring)

Molecular genetic testing, specifically for the HBA1 and HBA2 genes, is a critical procedure aimed at identifying mutations associated with various hemoglobin disorders. These genes are located on chromosome 16 within the alpha globin locus and play a vital role in the production of hemoglobin, the protein responsible for oxygen transport in the blood. The most prevalent condition linked to mutations in these genes is alpha thalassemia, which arises from the absence or reduction of alpha globin chain production due to deletions affecting the alpha A genes, including both HBA1 and HBA2. There are several known variants of alpha thalassemia, including Southeast Asian, Thai, Filipino, Mediterranean, and specific deletions such as alpha3.7, alpha4.2, and alpha20.5, as well as the Constant Spring variant, which is characterized by a mutation that elongates the protein structure by 31 amino acids. The inheritance pattern of these disorders is autosomal recessive, meaning that individuals must inherit mutations from both parents to develop significant 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 and is associated with severe complications such as fetal edema and anemia, and Hemoglobin H disease, which results from the loss of three alpha genes and presents with moderate anemia and splenomegaly. Additionally, carrier states may exhibit mild anemia, often misdiagnosed as iron deficiency anemia, while silent carriers may show no symptoms or only very mild changes in blood parameters. Molecular genetic testing is particularly indicated for individuals exhibiting symptoms of hemoglobin disorders, women with a history of fetal loss linked to hydrops fetalis syndrome, or those with a family history of these conditions.