Thalassemia Symptoms: Treatment and Types & Causes

Thalassemia Symptoms

Thalassemia is a disorder of the blood where the body fails to produce sufficient hemoglobin, causing a deficiency of red blood cells. The symptoms of thalassemia may differ based on the type and severity of the condition. Some of the common symptoms are:

• Fatigue and Weakness
• Paleness (Pallor)
• Jaundice
• Frequent Infections
• Delayed Growth
• Bone Deformities
• Enlarged Spleen and Liver (Splenomegaly and Hepatomegaly)
• Heart Problems
• Abdominal Pain
• Iron Overload

Thalassemia Treatment

Treatment of thalassemia varies with the type and severity of the disease, with a view to controlling symptoms and averting complications. The following are the main treatment methods:

Blood Transfusions

Regular Blood Transfusions: This is the primary treatment for severe thalassemia (like beta thalassemia major). Transfusion of blood provides the body with healthy red blood cells and keeps hemoglobin levels normal.

Iron Chelation Therapy

Purpose: Recurrent blood transfusions can cause iron accumulation in the body, which harms organs such as the heart and liver. Iron chelation therapy removes excess iron from the body.

Folic Acid Supplements

Folic acid is needed for red blood cell production. Patients with thalassemia are usually prescribed folic acid supplements to facilitate the production of healthy red blood cells.

Bone Marrow or Stem Cell Transplant (Hematopoietic Stem Cell Transplantation)

Cure for Some: A bone marrow or stem cell transplant can provide a possible cure for thalassemia, particularly in children. The procedure is to replace the patient's bone marrow with healthy marrow from a matching donor.

Gene Therapy (Experimental)

Gene Therapy is a new form of treatment that seeks to repair the genetic mutation responsible for thalassemia. It is currently at the research stage but holds hope as a future cure.

Splenectomy

In certain situations, patients with thalassemia require splenectomy (spleen removal) if their spleen enlarges (splenomegaly) and leads to issues such as infections, pain, or excess red cell destruction.

Types of Thalassemia

Thalassemia is divided into two broad categories depending on which component of the hemoglobin molecule is involved: alpha-thalassemia and beta-thalassemia. Both types have subtypes that range in severity.

Alpha Thalassemia

• Cause: This condition results from an issue with the production of the alpha-globin chains of hemoglobin. Hemoglobin consists of two alpha-globin and two beta-globin chains.
• Genetics: The gene responsible for producing alpha-globin is on chromosome 16. The severity of alpha thalassemia varies with the number of the four alpha-globin genes affected.

Beta Thalassemia

• Cause: It results from mutations in the beta-globin chain of hemoglobin. The beta-globin chains are needed to create hemoglobin, the oxygen-carrying protein in the blood.
• Genetics: The beta-globin gene lies on chromosome 11. Beta thalassemia is most commonly inherited in an autosomal recessive manner (both parents must give the gene for the condition to become apparent).

Causes of Thalassemia

Thalassemia results from genetic deletions or mutations in the genes that code for the production of hemoglobin, the protein within red blood cells that transports oxygen to the body. The cause is specific depending on whether the alpha-globin or beta-globin gene is involved, as thalassemia can be divided into alpha-thalassemia or beta-thalassemia depending on the globin chain involved.

Following is a division of the causes of thalassemia:

• Genetic Inheritance (Autosomal Recessive Inheritance)
• Gene Mutations
• Geographic and Ethnic Factors
• Carrier State
• Consanguinity

Thalassemia Diagnosis

Thalassemia is diagnosed on the basis of clinical assessment, history, and laboratory investigations. Diagnosis is established by finding typical changes in the blood and genetic testing. Following are the typical steps for the diagnosis of thalassemia:

Medical History and Physical Examination

• Medical History
• Physical Examination

Blood Tests

• Complete Blood Count (CBC)
• Peripheral Blood Smear
• Hemoglobin Electrophoresis
• Iron Studies

Genetic Testing

• DNA Analysis

Thalassemia in Children

• Thalassemia in children is a genetic blood disorder where the body makes an abnormal type or insufficient quantity of hemoglobin, resulting in anemia and other complications. It usually becomes apparent during the first two years of life, particularly in more severe cases such as beta thalassemia major.

Thalassemia Genetic Disorder

• Thalassemia is an inherited genetic disorder of the blood that impairs the synthesis of hemoglobin, the red blood cell protein that carries oxygen. Thalassemia is an autosomal recessive genetic disorder, meaning it is inherited from parents to offspring by genes on non-sex chromosomes.

What Makes Thalassemia a Genetic Disorder?

• Cause: Mutations in the globin genes—alpha-globin (HBA1 and HBA2) or beta-globin (HBB) genes.

These mutations lead to:

• Decreased production (thalassemia trait or minor) or
• Total absence (thalassemia major) of one of the globin chains that constitute hemoglobin.

Thalassemia Blood Disorder

Thalassemia is an inherited blood disease that interferes with the production of normal hemoglobin, required to transport oxygen in red blood cells. As a result, anemia ensues, such that there aren't sufficient good red blood cells to deliver a sufficient amount of oxygen to body tissues.

Why It's a Blood Disorder

Thalassemia falls under the blood disorder category as it has direct impacts on:

• Red blood cell production
• The formation of hemoglobin
• Carrying oxygen via the bloodstream

How Thalassemia Impacts Blood

Hemoglobin consists of two protein chains:

• Alpha chains
• Beta chains

In thalassemia, gene mutations that affect these chains lead to:

• Decreased or no production of alpha or beta chains
• Unstable hemoglobin, which causes breakdown of red blood cells
• Ineffective erythropoiesis (red blood cell production in the bone marrow)

Thalassemia Management

Thalassemia treatment is aimed at managing symptoms, avoiding complications, and enhancing quality of life—particularly in cases that are moderate to severe. There is no cure for thalassemia as of yet (other than in certain instances involving a bone marrow transplant), so treatment is generally lifelong.

Key Goals of Thalassemia Management

• Maintain proper hemoglobin levels
• Prevent and manage complications (particularly iron overload)
• Promote growth and development (in children)
• Enhance overall quality of life

Thalassemia Prevention

Thalassemia prevention involves prevention of transmission of the disease to offspring since thalassemia is a hereditary genetic condition. Even though thalassemia proper cannot be avoided after being born with it, occurrence among offspring can be eliminated or reduced using awareness, screening, and aware reproductive planning.

Important Steps toward Preventing Thalassemia

Carrier Screening (During or Before Pregnancy)

• Who to screen: Those with a family history of thalassemia, or from high-risk ethnic groups (e.g., Mediterranean, Middle Eastern, South Asian, Southeast Asian).
• What it detects: Whether an individual is a carrier of a mutated alpha or beta globin gene.
• Outcome: If both parents are carriers, there's a 25% chance with each pregnancy that the child will have thalassemia major.

Genetic Counselling

Assists couples to:

• Understand their carrier status
• Risk of passing on thalassemia to offspring
• Reproductive options available

Prenatal Testing

Can help identify if a fetus has thalassemia:

• Chorionic Villus Sampling (CVS) – performed at 10–12 weeks
• Amniocentesis – performed at 15–18 weeks

If the fetus is affected, parents can be well informed about the pregnancy

Preimplantation Genetic Diagnosis (PGD) with IVF

• Applied by carrier couples who are having in vitro fertilization (IVF)
• Embryos are screened for thalassemia before being implanted
• Only normal embryos (unaffected by thalassemia) are transferred

Public Awareness and Education

• Educating populations, particularly in high-risk areas, about:
• The genetic character of thalassemia
• The significance of carrier testing prior to marriage or pregnancy

Forced Screening Programs (in a few countries)

A few countries (e.g., Cyprus, Iran, Greece, and Italy) have national thalassemia prevention programs including:

• Premarital screening
• Genetic counselling
• Prenatal diagnosis service