ABNORMAL HEMOGLOBIN TRAITS

There are more than 400 unusual hemoglobin (Hb) genes associated with sickle cell disease and other hemoglobin variants. In the United States, millions carry a trait (one usual hemoglobin A gene, and one of the 22 most common sickle hemoglobin genes. The three most common sickle traits worldwide are S trait (Hb AS), C trait (Hb AC) and Beta Thalassemia trait (Hb β-Thalassemia), and Alpha Thalassemia (Hb α-Thalassemia).

Sickle Cell Traits, worldwide with a prevalence greater than one percent (1%) of a given population.

Hemoglobin Traits S,C, D, e & β Thalassemia

ABOUT SICKLE CELL DISEASE

Sickle Cell Disease is a genetically inherited blood disorder prevalent among people of African, Caribbean, Central/South American, East Indian, Middle Eastern, Mediterranean, Asian and Southeast Asian ancestry. Sickle cell trait and disease is indigenous to all these populations because of malaria. These genetic mutations developed over thousands of years as a result of the human body’s natural immune response against malaria.

In some cases, beginning as early as the age of 6 months, individuals with sickle cell disease can experience frequent, severe painful episodes that require multiple hospitalizations for treatment. It is common to spend weeks, sometimes months in the hospital for excruciating crisis episodes, especially when accompanied by other complications. Even in the case of adequate medical care, severe disability or death may result in childhood and early adult years.

The disease process results in severe anemia, oxygen deprivation, poor circulation and extreme pain. Painful episodes known as “crisis” are disabling and debilitating.

Major organs can suffer ischemic damage due to the restriction of blood flow. The heart, lungs, brain, as well as upper and lower extremities.

Complications associated with sickle cell disease are:

· Acute Chest Syndrome – a generalized term for respiratory dysfunction.

· Enlargement and damage of the spleen (life threatening, especially in children).

· Arm and leg ulcers caused by deep vein thrombosis (blood clots) that impede blood flow and cause edema (accumulation of fluid in tissue – swelling).

· Stroke due to infarction of blood vessels in the brain.

· Dysfunction or acute failure of the liver or kidneys.

· Retinopathy – detachment of the retina, which can cause visual impairment or blindness.

· Avascular Necrosis (AVN) is a degenerative complication affecting the bones and joints of the shoulders and hips. AVN is caused by diminished blood flow and loss of oxygen (ischemic damage). In the most advanced state of necrosis, hip and/or shoulder replacements are required.

Organs most commonly affected are the heart, lungs, brain, as well as upper and lower extremities – resulting in the development of arm and leg ulcers. Stroke due to infarction of blood vessels.
Enlargement and damage of the spleen (life threatening, especially in children).
Dysfunction or acute failure of the liver or kidneys.
Damage to tissue and bone due to diminished blood flow and loss of oxygen (ischemic damage). Avascular Necrosis is a degenerative complication affecting the shoulders and hips bones. In the most advanced state hip and shoulder replacements are required.

ABOUT THALASSEMIA

Thalassemia, like sickle Cell, is characterized as a group of abnormal hemoglobin variants.  The two most common types of thalassemia are Alpha Thalassemia (Cooley’s Anemia), beta (β) thalassemia.

Alpha Thalassemia, also known as Cooley’s Anemia is a genetic disorder, which produces severe anemia due the low production of alpha (α)-globin beta proteins in the hemoglobin molecule of red blood cells. α-thalassemia is a quantitative disorder.  Red blood cells (RBC) break down (hemolysis) every day, and the bone marrow is unable to produce enough RBCs to replace cells that are lost, resulting in severe anemia.  People who inherit alpha thalassemia must be regularly transfused to maintain good health. 

Βeta Thalassemia, beta (β)-globin proteins in the hemoglobin. β thalassemia symptoms include jaundice, extreme fatigue, enlargement of the heart and liver, bone deformation, damage to organs and organ systems. Individuals with β thalassemia are also prone to developing diabetes. Children diagnosed with β thalassemia require regular blood transfusions to maintain good health and survive. a Thalassemia also known as hemoglobin H disease (Hb AH) is a milder condition.

The thalassemia hemoglobin variants are present in Africa (N.E. Africa), S.E. Asia, China, India, Greece, Italy, Eastern Europe, and the Middle Eastern countries.

ABOUT RARE DISORDERS

In the United States, a rare disease is defined as a condition that affects fewer than 200,000 people. This definition was created by Congress in the Orphan Drug Act of 1983. Rare diseases became known as orphan diseases because drug companies were not interested in adopting them to develop treatments. The Orphan Drug Act created financial incentives to encourage companies to develop new drugs for rare diseases. The rare disease definition was needed to establish which conditions would qualify for the new incentive programs.

The definition of rare disease is different in other countries. In the European Union, rare disease is defined as affecting fewer than 1 in 2,000 people. 

The United States has identified 7,000 rare diseases, affecting between 25-30 million The Rare Disease Community uses this estimate to bring attention to the large impact on individuals and families across the nation. 

Most rare diseases are not tracked in the United States.  The few types of rare diseases that are tracked when a person is diagnosed are identified through NIH funded Newborn Screening Programs nationally. State newborn screenings tests track for metabolic disorders, genetically inherited disorders, birth defects, cancers, and certain infectious diseases.

To learn more about rare diseases visit the GARD (Genetic and Rare Diseases Information Center at NIH.