Thalassemias are a group of inherited blood disorders that can lead to anemia due to changes in the hemoglobin genes that affect red blood cell formation. Hemoglobin is the protein in red blood cells that carries oxygen. Without enough hemoglobin, red blood cells may not live as long or work as well, which can contribute to anemia. Thalassemia is rare, affecting only 1.7% of the world's population. The outlook for thalassemia depends on the type and severity of the condition; various medical approaches can be used to help improve the overall quality of life for those who need support. (1-3)
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What is Thalassemia?
Adult hemoglobin consists of an iron-containing heme ring and four globin chains: two alpha and two beta chains. Changes in the genes that code for either the alpha- or beta-hemoglobin chains can result in abnormal production of these protein chains, leading to low hemoglobin levels and microcytic anemia, which is characterized by small red blood cells (RBCs). (3)
Thalassemia is an inherited blood disorder, meaning a gene change is passed on from at least one parent. The type and number of inherited gene changes determine the type and severity of the condition.
What is Alpha-Thalassemia?
Alpha-thalassemia results from gene deletions coding for the alpha-hemoglobin chain and causes a decrease in the rate of alpha-chain synthesis. Four genes are responsible for the alpha chain, and the severity of alpha-thalassemia depends on the number of gene changes present. (3)
A single gene change results in silent carrier status. A person who is a silent carrier will have normal blood work findings and will not show symptoms of thalassemia. They can pass the gene change on to future children. (4)
A double gene deletion causes alpha-thalassemia trait. Lab work may show no changes to RBCs or mild microcytic anemia. People with two gene changes are generally without symptoms. (2)
Alpha-thalassemia intermedia, or hemoglobin H disease, results from three gene changes. Moderate-to-severe microcytic anemia with increased breakdown (hemolysis) of RBCs and spleen enlargement can occur. (2)
Alpha-thalassemia major results from four gene deletions and is the most severe form of alpha-thalassemia. This severe anemia is generally not compatible with life and often results in the baby's death before birth. (4)
What is Beta-Thalassemia?
Beta-thalassemia results from one or two gene changes that control the synthesis of the beta-hemoglobin chain, thereby slowing beta-chain production. Beta-thalassemia minor results from one gene defect; mild microcytic anemia may be present on lab work, but commonly the person is without symptoms. Two gene changes can lead to either beta-thalassemia intermedia or beta-thalassemia major, depending on the resulting extent of decreased beta-chain synthesis. People with beta-thalassemia intermedia and major are without symptoms at birth; however, symptoms may begin to develop around six months of age. Moderate-to-severe anemia can develop, along with other thalassemia-related health challenges. (2, 5)
Thalassemia Symptoms
Anemia in thalassemia results from ineffective RBC formation and increased hemolysis of the RBCs in circulation. Thalassemia minor is usually without symptoms and has a good outlook, but thalassemia major is a severe condition and can cause many symptoms (6):
- Difficulty breathing
- Dizziness
- Fatigue
- Feeling cold
- Headaches
- Pale skin
- Weakness
More symptoms may develop over time (usually presenting by age two) in the more severe types of thalassemia, especially beta-thalassemia major (2, 3, 6):
- Abdominal swelling caused by liver and spleen enlargement
- Dark urine
- Irritability
- Skeletal deformities
- Slowed growth and development
- Jaundice (yellow skin)
Complications of Thalassemia
Various health challenges are associated with moderate-to-severe thalassemia (3, 7):
- Bone Deformities: thalassemia can make bone marrow expand, causing a widening of bones. Structural changes are common in the face and skull, referred to as a "chipmunk face" appearance. Brittle bones that result from these changes increase the risk of bone breaks.
- Gallstones: increased RBC hemolysis can lead to chronic bilirubin elevations, a breakdown product of RBCs; this predisposes a person to gallstone formation.
- Increased Risk of Infection: especially in people with a history of splenectomy (surgical removal of the spleen)
- Iron Overload can occur from frequent therapeutic blood transfusions and increased hemolytic events. Excess iron deposition can contribute to increased oxidative stress in the body, potentially affecting various body systems and causing: skin discoloration, abnormal heart rate and heart function, chronic joint pain, enlargement of the spleen and liver (hepatosplenomegaly), liver challenges, blood sugar imbalances, thyroid function changes, and early-onset movement disorders.
How Is Alpha Thalassemia Diagnosed?
A complete blood count (CBC) may be ordered as part of routine blood work and show signs of thalassemia incidentally or is the first test ordered in a suspected case of thalassemia. A CBC with low hemoglobin and MCV (indicating microcytic anemia) suggests thalassemia.
A peripheral blood smear, a microscopic analysis of RBCs, is virtually diagnostic of thalassemia and will report findings of many small, pale RBCs varying in size and shape.
The reticulocyte count, a measurement of immature RBCs in circulation, is often elevated in thalassemia.
Hemoglobin electrophoresis evaluates the type and amounts of hemoglobin present in RBCs. Characteristic patterns of hemoglobin configurations can help identify the various types of thalassemia.
Genetic analysis confirms changes in the alpha- and beta-protein genes. This is not routinely needed for diagnosis but can be used to help identify or determine genetic carrier status.
Other Lab Tests to Check
Tests to rule out other causes of microcytic anemia:
- An iron study to rule out iron deficiency anemia (IDA)
- Porphyrin acts as the framework for the heme portion of hemoglobin. Porphyrin levels can help differentiate between beta-thalassemia minor from anemia due to lead exposure or iron deficiency. Porphyrin levels are normal in beta-thalassemia but elevated in the latter conditions. (3)
Routine screening for thalassemia-related challenges should be performed. Examples of tests and imaging that may be ordered include:
- Thyroid panel
- Comprehensive metabolic panel (CMP) to monitor the gallbladder, liver, and bilirubin levels
- Folate levels can be checked as folate deficiency is more common in alpha-thalassemia major and intermedia (2). Serum folate and RBC folate can be used to assess folate nutritional status.
- Abdominal ultrasound to monitor the gallbladder, liver, and spleen
- MRI imaging of the heart
How Is Alpha Thalassemia Managed?
Regular blood transfusions are a common approach for patients with thalassemia major. However, iron overload, which can lead to increased oxidative stress and organ challenges, is a common side effect of frequent transfusions. Therefore, pharmacologic iron-chelating agents are used to help manage excess iron in the body. (2)
Stem cell transplantation and splenectomy (surgical removal of the spleen) are other conventional options for those with thalassemia major (2).
Functional Medicine Approaches for Thalassemia
In one study, 90% of patients with thalassemia reported using complementary and alternative medicine (CAM) at least once in managing their condition. Evidence-based CAM approaches applicable to thalassemia management include:
- Drinking black tea to potentially reduce iron absorption from the digestive tract (3)
- Supplemental folic acid to help address folate deficiency in patients with thalassemia major (2)
- L-Carnitine deficiency is associated with anemia, cardiovascular challenges, and muscle weakness. Total carnitine levels may be 50-60% lower in children and adults with thalassemia major than in healthy controls. These findings suggest that L-carnitine supplementation may support RBC integrity and help manage thalassemia-related challenges.
- Antioxidant support can help manage damage to the RBC membrane caused by increased oxidative stress in thalassemia patients. Vitamins E and C have been specifically researched as supportive interventions in thalassemia patients.
- Psychological support and education related to acceptance and expectations of chronic conditions can significantly improve patient well-being.
Healthy living habits in conjunction with conventional approaches can aid in managing thalassemia:
- Avoid excess iron in supplements and vitamins to help manage iron levels
- When possible, avoid non-steroidal anti-inflammatory drugs (NSAIDs), which can contribute to oxidative stress and hemolysis
- Eat a healthy diet to get adequate amounts of calcium, vitamin D, B vitamins, and protein, which are nutrients that support RBC and bone health
- Wash hands frequently to help prevent illness
Summary
Thalassemia is an inherited blood disorder caused by changes in hemoglobin genes, resulting in microcytic and hemolytic anemia. The outlook for thalassemia varies, dictated by the number and type of gene changes. Identifying thalassemia can provide insight into genetic carrier status and guide management considerations. While some people may not require any specific interventions, blood transfusions and iron management are common approaches for those who do. Functional medicine can offer additional options to support the whole person, aligning with conventional goals and helping to manage condition-related challenges.
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