Alpha globin is a protein component of hemoglobin, the protein in red blood cells that transports oxygen throughout the body. Its proper function is essential for ensuring oxygen reaches all tissues and organs.
Understanding Alpha Globin and Hemoglobin
Alpha globin is a polypeptide chain, a string of amino acids that folds into a specific three-dimensional shape. In adult hemoglobin, known as HbA, two alpha globin chains combine with two beta globin chains. Each of these four globin chains then associates with a “heme” group, a non-protein component containing an iron atom.
This assembly forms a complete hemoglobin molecule, a tetramer with four subunits. The iron atom within each heme group is where oxygen molecules bind. A single hemoglobin molecule can carry up to four oxygen molecules, one per heme group.
Hemoglobin’s function is to bind oxygen in the lungs and release it to tissues throughout the body. It also transports carbon dioxide back to the lungs for exhalation. Alpha globin chains contribute to hemoglobin’s stability and function, influencing its ability to bind and release oxygen. This process is regulated by factors like pH and carbon dioxide levels, which alter hemoglobin’s affinity for oxygen.
The Genes Behind Alpha Globin
Alpha globin protein production is controlled by specific genes. Humans possess two functional copies of the alpha globin gene on each chromosome 16, totaling four alpha globin genes (HBA1 and HBA2). These genes are situated closely together in the alpha-globin locus.
Each person inherits two copies of chromosome 16, one from each parent. These genes contain the genetic code for synthesizing alpha globin proteins. The process begins with transcription, where genetic information is copied into messenger RNA (mRNA), followed by translation, where ribosomes use the mRNA to build the alpha globin chains.
While HBA1 and HBA2 genes produce identical alpha globin proteins, variations or deletions within these genes can affect the amount produced. Such genetic changes can lead to reduced or absent alpha globin chains, impacting functional hemoglobin formation. This can result in various conditions associated with alpha globin abnormalities.
Conditions Related to Alpha Globin Problems
When alpha globin production is impaired, it can lead to inherited blood disorders known as alpha thalassemia. The severity depends on the number of non-functional or deleted alpha globin genes. There are four main forms, each with varying clinical presentations.
Silent Carrier State
The mildest form is the “silent carrier” state, where one of the four alpha globin genes is missing or non-functional. Individuals with this condition have no symptoms and blood tests appear normal, though their red blood cells may be slightly smaller. Silent carriers can pass the affected gene to their children.
Alpha Thalassemia Trait
When two alpha globin genes are affected, it results in alpha thalassemia trait, also known as alpha thalassemia minor. People with this condition may experience mild anemia, characterized by fatigue or reduced exercise tolerance, but may have no noticeable symptoms. Their red blood cells are smaller and paler than normal.
Hemoglobin H (HbH) Disease
Hemoglobin H (HbH) disease occurs when three of the four alpha globin genes are missing or non-functional. This leads to moderate to severe anemia, with symptoms such as fatigue, yellowish skin (jaundice), an enlarged spleen or liver, and leg ulcers. Individuals with HbH disease may experience worsening symptoms during fevers or exposure to certain medications, chemicals, or infections. Management involves daily folic acid supplements, and some individuals may require occasional blood transfusions to manage severe anemia, which can lead to iron overload.
Alpha Thalassemia Major
The most severe form, alpha thalassemia major, also known as Hb Bart’s hydrops fetalis syndrome, involves the deletion or inactivation of all four alpha globin genes. This condition results in a complete absence of alpha globin chains, leading to the formation of an abnormal hemoglobin called Hb Bart’s, which cannot effectively carry oxygen. Affected fetuses develop severe anemia and fluid accumulation (hydrops fetalis), leading to stillbirth or death shortly after birth.
Diagnostic methods for alpha thalassemia include complete blood counts (CBC) to assess red blood cell size and hemoglobin levels, along with specialized hemoglobin analysis and genetic testing to identify specific gene deletions or mutations.