The hemoglobinopathies are a group of disorders passed down through families (inherited) in which there is abnormal production or structure of the hemoglobin molecule. Sickle cell disease (SCD) is one such blood disorder caused by the abnormal hemoglobin that damages and deforms red blood cells. The abnormal red cells break down, causing anemia, and obstruct blood vessels, leading to recurrent episodes of severe pain and multi-organ ischemic damage. SCD affects millions of people throughout the world and is particularly common among people whose ancestors come from sub-Saharan Africa, regions in the Western Hemisphere (South America, the Caribbean, and Central America); Saudi Arabia; India; and Mediterranean countries such as Turkey, Greece and Italy. There is no widely available cure for SCD although some children have been successfully treated with blood stem cell, or bone marrow, transplants. However, hematopoietic stem cell transplant is not widely done for SCD, because of the difficulty in finding a matched donor. Therefore, the number of people with SCD who get transplants is low. In addition, there are several complications associated with the procedure, including death in about 5 percent of people. In SCD, clinical severity varies, ranging from mild and sometimes asymptomatic states to severe symptoms requiring hospitalization. Symptomatic treatments exist, and newborn screening (NBS) for SCD can reduce the burden of the disease on affected newborns and children.

Thalassemia is another type of blood disorder that is caused by a defect in the gene that helps control the production of the globin chains that make up the hemoglobin molecule. There are two main types of thalassemia:

• Alpha thalassemia occurs when a gene or genes related to the alpha globin protein are missing or changed (mutated). Alpha thalassemias occur most often in persons from Southeast Asia, the Middle East, China and in those of African descent.
• Beta thalassemia occurs when a beta globin gene is changed (mutated) so as to affect production of the beta globin protein.
• Beta thalassemias occur most often in persons of Mediterranean origin. To a lesser extent, Chinese, other Asians and African Americans can be affected.

The following table summarizes the affected populations, prevalence, and outcomes of common hemoglobinopathies. These hemoglobinopathies may either falsely raise or lower A1C results, depending on the variant and the assay method.

Common hemoglobinopathies: populations affected, prevalence, and outcomes

Hemoglobin C disease is a condition affecting a protein in the blood (hemoglobin) which transports oxygen throughout the body. Symptoms of this condition can include fatigue, weakness, and anemia. The spleen can also become enlarged as a result of this disease. For many people with this condition, symptoms are relatively mild and the lifespan is normal. Some people with this condition do not exhibit any symptoms at all. Treatment for any symptoms that do present include taking folic acid supplements.

Hemoglobin C disease is caused by a mutation in the gene that provides instructions to the body to make hemoglobin. This mutation causes a change in the shape of the red blood cells so that oxygen isn't carried as well throughout the body.

Hemoglobin E (HbE) disease is a mild, inherited blood disorder characterized by an abnormal form of hemoglobin, called hemoglobin E. People with this condition may have very mild anemia, but the condition typically does not cause any symptoms. It is inherited in an autosomal recessive manner and is caused by a mutation in the HBB gene. The mutation that causes hemoglobin E disease primarily occurs in Southeast Asian populations, and rarely in Chinese populations. Most people with HbE disease do not need any treatment.

Hemoglobin (Hb) Zurich is an inherited blood disorder. People with Hb Zurich have an abnormal form of Hb, a red blood cell (RBC) protein that binds to oxygen in the lungs. This abnormal Hb more readily binds to carbon monoxide (producing carboxyhemoglobin or COHb). Normally the level of COHb is less than 1-2% in adults. People with Hb Zurich tend to have COHb levels above 3%. The health effects of Hb Zurich tend to be mild compared to other inherited blood cell disorders. Symptoms usually develop only when the body is stressed due to an infection or fever or when exposed to certain drugs. Symptoms develop as a result of the premature breakdown of RBC (hemolytic anemia).