5 minute read


Definition, Description, Causes and symptoms, Diagnosis, Treatment, Prognosis, Prevention

Hemoglobinopathies are genetic (inherited) disorders of hemoglobin, the oxygen-carrying protein of the red blood cells.


The hemoglobin molecule is composed of four separate polypeptide chains of amino acids, two alpha chains and two beta chains, as well as four iron-bearing heme groups that bind oxygen. The alpha chains are coded for by two similar genes on chromosome 16; the beta chains by a single gene on chromosome 11. Mutations and deletions in these genes cause one of the many hemoglobinopathies.

In general, hemoglobinopathies are divided into those in which the gene abnormality results in a qualitative change in the hemoglobin molecule and those in which the change is quantitative. Sickle cell anemia (sickle cell disease) is the prime example of the former, and the group of disorders known as the thalassemias constitute the latter. It has been estimated that one third of a million people worldwide are seriously affected by one of these genetic disorders.

Causes and symptoms

Sickle cell anemia (SSA), an autosomal recessive disorder more common in the Black population, is caused by a single mutation in the gene that codes for the beta polypeptide. Approximately 1/400 to 1/600 African-Americans are born with the disorder, and, one in ten is a carrier of one copy of the mutation. In certain parts of the African continent, the prevalence of the disease reaches one in fifty individuals.

The sickle cell mutation results in the substitution of the amnio acid, valine, for glutamic acid in the sixth position of the beta polypeptide. In turn, this alters the conformation of the hemoglobin molecule and causes the red blood cells to assume a characteristic sickle shape under certain conditions. These sickle-shaped cells, no longer able to pass smoothly through small capillaries, can block the flow of blood. This obstruction results in symptoms including growth retardation, severe pain crises, tissue and organ damage, splenomegaly, and strokes. Individuals with SSA are anemic and prone to infections, particularly pneumonia, a significant cause of death in this group. Some or all of these symptoms are found in individuals who have the sickle mutation in both copies of their beta-globin gene. Persons with one abnormal gene and one normal gene are said to be carriers of the sickle cell trait. Carriers are unaffected because of the remaining normal copy of the gene.

The thalassemias are a diverse group of disorders characterized by the fact that the causative mutations result in a decrease in the amount of normal hemoglobin. Thalassemias are common in Mediterranean populations as well as in Africa, India, the Mideast, and Southeast Asia. The two main types of thalassemias are alpha-thalassemia due to mutations in the alpha polypeptide and beta-thalassemia resulting from beta chain mutations.

Since individuals possess a total of four genes for the alpha polypeptide (two genes on each of their two chromosomes 16), disease severity depends on how many of the four genes are abnormal. A defect in one or two of the genes has no clinical effect. Abnormalities of three results in a mild to moderately severe anemia (hemoglobin H disease) and splenomegaly. Loss of function of all four genes usually causes such severe oxygen deprivation that the affected fetus does not survive. A massive accumulation of fluid in the fetus (hydrops fetalis) results in stillbirth or neonatal death.

Beta thalassemias can range from mild and clinically insignificant (beta thalassemia minor) to severe and life-threatening (beta thalassemia major, also known as Cooley's anemia), depending on the exact nature of the gene mutation and whether one or both copies of the beta gene are affected. While the milder forms may only cause slight anemia, the more severe types result in growth retardation, skeletal changes, splenomegaly, vulnerability to infections, and death as early as the first decade of life.


Many countries, including the United States, have made concerted efforts to screen for sickle cell anemia at birth because of the potential for beginning early treatment and counseling parents about their carrier status. Diagnosis is traditionally made by blood tests including hemoglobin electrophoresis. Similar tests are used to determine whether an individual is a sickle cell or thalassemia carrier. In certain populations with a high prevalence of one of the mutations, carrier testing is common. If both members of a couple are carriers of one of these conditions, it is possible through prenatal genetic testing to determine if the fetus will be affected, although the severity of the disease cannot always be predicted.


Treatment of SSA has improved greatly in recent years with a resulting increase in life expectancy. The use of prophylactic (preventative) antibiotic therapy has been particularly successful. Other treatments include fluid therapy to prevent dehydration, oxygen supplementation, pain relievers, blood transfusions, and several different types of medications. Recent interest has focused on bone marrow transplantation and future directions include the possibility of gene replacement therapy.

Since the clinically important thalassemias are characterized by severe anemia, the traditional treatment has been blood transfusion, but the multiple transfusions needed to sustain life lead to an iron overload throughout the tissues of the body and eventual destruction of the heart and other organs. For this reason, transfusion therapy must also include infusions of medications such as deferoxamine (desferroxamine) to rid the body of excess iron. As with sickle cell anemia, bone marrow therapy has been successful in some cases.


Hemoglobinopathies are life-long disorders. The prognosis depends upon the exact nature of the mutation, the availability of effective treatment, as well as the individual's compliance with therapies.


Because the hemoglobinopathies are inherited diseases, primary prevention involves carriers making reproductive decisions to prevent passage of the abnormal gene to their offspring. At present, most prevention is targeted toward the symptoms using treatments such as those described above.



Behrman, Richard E. et al. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, W. B. Saunders, 2000.

Jorde, Lynn B. et al. Medical Genetics. 2nd ed. New York: Mosby, 1999.


Olivieri, Nancy F. "The beta-Thalassemias." The New England Journal of Medicine July 1999, 341(2): 99-109.

Epstein, Franklin H."Pathogenesis and Treatment of Sickle Cell Disease." The New England Journal of Medicine September 1997, 337(11): 762-769.


American Sickle Cell Anemia Association. <http://www.ascaa.org>.

Sickle Cell Disease Association of American, Inc. <http://sicklecelldisease.org>.

The Sickle Cell Information Center. http://www.emory.edu. PO Box 109, Grady Memorial Hospital, 80 Bulter Street, SE, Atlanta, GA 30303, 404-616-3572.

Sallie Freeman, PhD


Autosomal recessive—A pattern of inheritance in which both copies of an autosomal gene must be abnormal for a genetic condition or disease to occur. An autosomal gene is a gene that is located on one of the autosomes or non-sex chromosomes. When both parents have one abnormal copy of the same gene, they have a 25% chance with each pregnancy that their offspring will have the disorder.

Splenomegaly—Enlargement of the spleen.

Additional topics

Health and Medicine EncyclopediaHealth and Medicine Encyclopedia - Vol 12