Thalassemias are a group of inherited blood disorders that cause anemia because of mutations of the hemoglobin genes that result in ineffective red blood cell formation. Hemoglobin is the protein in red blood cells that carries oxygen. Red blood cells live shorter and don't function properly without sufficient hemoglobin, causing anemia. Thalassemia is rare, affecting only 1.7% of the world's population. Thalassemia prognosis depends on the type and severity of the disease; conventional and functional medicine modalities can be implemented in those who require treatment to improve their overall quality of life. (1-3)
What is Thalassemia?
Adult hemoglobin consists of an iron-containing heme ring and four globin chains: two alpha and two beta chains. Mutations in the genes that code for either the alpha- or beta-hemoglobin chains can result in abnormal manufacturing of either protein chain; this results in low hemoglobin levels and microcytic anemia characterized by small red blood cells (RBCs). (3)
Thalassemia is an inherited blood disorder, meaning a gene mutation is passed on from at least one parent. The type and number of inherited gene mutations dictate the type and severity of the disease.
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 mutations present. (3)
A single gene mutation results in silent carrier status. A person who is a silent carrier will have normal blood work findings and will not present with symptoms of thalassemia. They can pass the gene mutation on to future children. (4)
A double gene deletion causes alpha-thalassemia trait. Lab work will reflect no changes to RBCs or mild microcytic anemia. People with two gene mutations are generally asymptomatic. (2)
Alpha-thalassemia intermedia, or hemoglobin H disease, results from three gene mutations. Moderate-to-severe microcytic anemia with increased destruction (hemolysis) of RBCs and spleen enlargement is the result. (2)
Alpha-thalassemia major results from four gene deletions and is the most severe form of alpha-thalassemia. This severe anemia is incompatible with life and generally results in the baby's death before birth. (4)
What is Beta-Thalassemia?
Beta-thalassemia results from one or two gene mutations 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 presents on lab work, but commonly the patient is asymptomatic. Two gene mutations 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 asymptomatic at birth; however, symptoms begin to develop around six months of age. Moderate-to-severe anemia develops, along with other thalassemia-related health complications. (2, 5)
Anemia in thalassemia results from ineffective RBC formation and increased hemolysis of the RBCs in circulation. Thalassemia minor is usually asymptomatic and has a good prognosis, but thalassemia major is a severe disease and can cause many symptoms (6):
- Difficulty breathing
- Feeling cold
- Pale skin
More symptoms 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
- Skeletal deformities
- Slowed growth and development
- Jaundice (yellow skin)
Complications of Thalassemia
Various health complications are associated with moderate-to-severe thalassemia (3, 7):
- Bone Deformities: thalassemia can make bone marrow expand, causing a widening of bones. Structural abnormalities are common in the face and skull, referred to as "chipmunk face" appearance. Brittle bones that result from these deformities 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 cause increased oxidative stress to the body, resulting in damage to various body systems and causing: skin discoloration, abnormal heart rate and heart failure, chronic joint pain, enlargement of the spleen and liver (hepatosplenomegaly), cirrhosis and liver failure, diabetes mellitus, hypothyroidism, and early-onset Parkinson's disease.
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 diagnose the various types of thalassemia.
Genetic analysis confirms mutations in the alpha- and beta-protein genes. This is not routinely needed for diagnosis but can be used to help diagnose 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 differentiate between beta-thalassemia minor from anemia due to lead poisoning or iron deficiency. Porphyrin levels are normal in beta-thalassemia but elevated in the latter conditions. (3)
Routine screening for thalassemia-related complications 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 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 Treated?
Regular blood transfusions are the standard treatment for patients with thalassemia major. However, iron overload, which can lead to increased oxidative stress and organ damage, is a common side effect of frequent transfusions. Therefore pharmacologic iron-chelating agents are used to remove excess iron from the body. (2)
Stem cell transplantation and splenectomy (surgical removal of the spleen) are other conventional treatment options for those with thalassemia major (2).
Functional Medicine Treatment for Thalassemia
In one study, 90% of patients with thalassemia reported utilizing complementary and alternative medicine (CAM) at least once in treating their disease. Evidence-based CAM therapies applicable to thalassemia management include:
- Drinking black tea to reduce iron absorption from the digestive tract (3)
- Supplemental folic acid to treat folate deficiency in patients with thalassemia major (2)
- L-Carnitine deficiency is associated with anemia, cardiovascular complications, 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 promote RBC integrity and mitigate thalassemia-related complications.
- Antioxidant therapy can combat damage to the RBC membrane caused by increased oxidative stress in thalassemia patients. Vitamins E and C have been specifically researched as therapeutic interventions in thalassemia patients.
- Psychological support and education related to acceptance and expectations of chronic disease can significantly improve patient well-being.
Healthy living habits in conjunction with conventional therapies can aid in managing thalassemia:
- Avoid excess iron in supplements and vitamins to prevent iron overload
- When possible, avoid non-steroidal anti-inflammatory drugs (NSAIDs), which can cause excessive 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 prevent illness
Thalassemia is an inherited blood disorder caused by hemoglobin gene mutations, resulting in microcytic and hemolytic anemia. The prognosis of thalassemia varies, dictated by the number and type of gene mutations. Diagnosis of thalassemia can provide insight into genetic carrier status and guide treatment recommendations. While some people may not require any treatment, blood transfusions and iron chelation are the standard therapies for those who do. Functional medicine can provide adjunctive treatment options to treat the whole person, supporting conventional therapy goals and preventing disease complications.
Lab Tests in This Article
1. CDC. (2020, May 14). What is Thalassemia? Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/thalassemia/facts.html
2. Muncie, H. L., & Campbell, J. (2009). Alpha and beta thalassemia. American Family Physician, 80(4), 339–344. https://www.aafp.org/pubs/afp/issues/2009/0815/p339.html
3. Bajwa, H., & Basit, H. (2022, August 8). Thalassemia. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK545151/
4. Alpha Thalassemia. (2019, November 19). Johns Hopkins Medicine. https://www.hopkinsmedicine.org/health/conditions-and-diseases/alpha-thalassemia
5. Beta Thalassemia. (2020, July 2). Johns Hopkins Medicine. https://www.hopkinsmedicine.org/health/conditions-and-diseases/beta-thalassemia
6. NIH. (2022b, June 1). Thalassemia Symptoms. National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/health/thalassemia/symptoms
7. Mayo Clinic. (2021, November 17). Thalassemia - Symptoms and Causes. https://www.mayoclinic.org/diseases-conditions/thalassemia/symptoms-causes/syc-20354995#:~:text=Thalassemia%20