Hemoglobin is made of iron (heme) and protein (globin). The function of hemoglobin is to carry oxygen from the lung to tissues. There are three main types of normal hemoglobin found in adults: Hemoglobin A, hemoglobin A2, and hemoglobin F are the types of globin molecule combinations, namely alpha, beta, gamma, or delta, determine the type of hemoglobin. All of the normal hemoglobin is a combination of alpha and non-alpha chains. The gene for alpha globin is located on chromosome 16. Hemoglobin A is composed of one pair of alpha-globin chains and one pair of beta-globin chains. It makes 95% to 98% of adult hemoglobin. Hemoglobin A2 is a pair of alpha chains and a pair of delta chains. It makes 1% to 3% of adult hemoglobin. Hemoglobin F is comprised of two alpha and two gamma chains. It makes up for the majority of neonatal hemoglobin, but in normal adults is 2% to 3% of the total hemoglobin. The percentages fluctuate based on age, genetics, medications, and underlying conditions.

Thalassemias are a group of disorders caused by abnormal production of globin chains. The production can be diminished or can be absent for one or more of the globin chains. This imbalance of globin chain production impairs the production of normal hemoglobin. This impairment causes ineffective erythropoiesis with intramedullary hemolysis. Alpha thalassemia refers specifically to the abnormal or absent manufacturing of alpha-globin chains. These are associated with more than 15 different genetic mutations. The severity of the clinical condition is based on the mutation type. The severity of mutation is based on which of the two alpha-globin loci is affected. Mutations can also be deletion or non-deletion. In deletion mutation, there is an inheritance of a single alpha-globin gene. With the non-deletion type, a patient has inherited two alpha-globin genes, but one gene carries a non-deletion abnormality, for example, point mutation. In non-deletion, the severity of clinical expression is also affected depending on whether the mutation blocks the production of the remaining normal alpha chains partially or fully. Hemoglobin H disease occurs when only one normal alpha gene has been inherited. One of these most common non-deletion subtypes of Hemoglobin H is called Hemoglobin Constant Spring. HbH disease tends to be more severe in patients with the non-deletion-type likely due to interference with the transcription of the normal alpha chain gene by the abnormal one.

Disclosure:Janine Harewood declares no relevant financial relationships with ineligible companies.

Disclosure:Alexandre Azevedo declares no relevant financial relationships with ineligible companies.