CPT® Code 81258

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

Molecular genetic testing is a critical procedure used to identify specific mutations in the HBA1 or HBA2 genes, which are responsible for encoding the alpha globin protein. These genes are located on chromosome 16 within the alpha globin locus and are integral to the production of hemoglobin, the protein in red blood cells that carries oxygen throughout the body. Various hemoglobin disorders are associated with mutations in these genes, with alpha thalassemia being the most prevalent worldwide. This condition arises from the absence or reduced production of alpha globin chains, often due to deletions affecting the HBA1 and HBA2 genes. There are several known variants of alpha thalassemia, including SEA, THAI, FIL, MED, and alpha20.5, which involve deletions of both genes 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. 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 due to the complete loss of all four alpha globin genes, and Hemoglobin H (HbH) disease, which results from the loss of three alpha genes. Symptoms of these conditions can range from severe anemia and fetal complications to mild anemia in carrier states. 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 genetic conditions.