Beta thalassemia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Beta thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the iron-containing protein in red blood cells that carries oxygen to cells throughout the body.

In people with beta thalassemia, low levels of hemoglobin reduce oxygen levels in the body. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications. People with beta thalassemia are at an increased risk of developing abnormal blood clots.

Beta thalassemia is classified into two types depending on the severity of symptoms: thalassemia major (also known as transfusion-dependent thalassemia or Cooley's anemia) and thalassemia intermedia (which is a non-transfusion-dependent thalassemia). Of the two types, thalassemia major is more severe.

The signs and symptoms of thalassemia major appear within the first 2 years of life. Children develop life-threatening anemia. They do not gain weight and grow at the expected rate (faltering weight) and may develop yellowing of the skin and whites of the eyes (jaundice). Affected individuals may have an enlarged spleen, liver, and heart, and their bones may be misshapen. Puberty is delayed in some adolescents with thalassemia major.

Many people with thalassemia major have such severe symptoms that they need frequent blood transfusions to replenish their red blood cell supply. Over time, an influx of iron-containing hemoglobin from chronic blood transfusions can lead to a buildup of iron in the body, resulting in liver, heart, and hormone problems.

Thalassemia intermedia is milder than thalassemia major. The signs and symptoms of thalassemia intermedia appear in early childhood or later in life. Affected individuals have mild to moderate anemia and may also have slow growth, bone abnormalities, and an increased risk of developing abnormal blood clots.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also known as mutations) in the HBB gene cause beta thalassemia. The HBB gene provides instructions for making a protein called beta-globin. Beta-globin is a component (subunit) of hemoglobin. Hemoglobin consists of four protein subunits, typically two subunits of beta-globin and two subunits of another protein called alpha-globin.

Some variants in the HBB gene prevent the production of any beta-globin. The absence of beta-globin is referred to as beta-zero (β0) thalassemia. Other HBB gene variants allow some beta-globin to be produced but in reduced amounts. A reduced amount of beta-globin is called beta-plus (β+) thalassemia. Having either β0 or β+ thalassemia does not necessarily predict disease severity, however; people with both types have been diagnosed with thalassemia major and thalassemia intermedia.

A shortage of beta-globin hinders the formation of functional hemoglobin. Without sufficient hemoglobin, red blood cells do not develop normally, causing a shortage of mature red blood cells. The low number of mature red blood cells leads to anemia and other associated health problems in people with beta thalassemia.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Thalassemia major and thalassemia intermedia are inherited in an autosomal recessive pattern, which means both copies of the HBB gene in each cell have variants. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition. Sometimes, however, people with only one HBB gene variant in each cell develop mild anemia. These mildly affected people are said to have thalassemia minor.

In a small percentage of families, the HBB gene variant is inherited in an autosomal dominant manner. In these cases, one copy of the altered gene in each cell is sufficient to cause the signs and symptoms of beta thalassemia.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Beta thalassemia is a fairly common blood disorder worldwide. Thousands of infants with beta thalassemia are born each year. Beta thalassemia occurs most frequently in people from Mediterranean countries, North Africa, the Middle East, India, Central Asia, and Southeast Asia.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal hemoglobin · Very frequent (99-80%)

Anomaly in the level or the function of hemoglobin, the oxygen-carrying protein of erythrocytes.

Abnormality of the skeletal system · Very frequent (99-80%)

An abnormality of the skeletal system.

Anemia · Very frequent (99-80%)

A reduction in erythrocytes volume or hemoglobin concentration.

Microcytic anemia · Very frequent (99-80%)

A kind of anemia in which the volume of the red blood cells is reduced.

Pallor · Very frequent (99-80%)

Abnormally pale skin.

Splenomegaly · Very frequent (99-80%)

Abnormal increased size of the spleen.

Abnormal skull morphology · Frequent (79-30%)

An abnormality of the skull, the bony framework of the head which is comprised of the neurocranium (with eight cranial bones) and the viscerocranium (facial skeleton) that comprises fourteen facial bones with the mandible as its largest bone.

Abnormality of iron homeostasis · Frequent (79-30%)

An abnormality of the homeostasis (concentration) of iron cation.

Other findings in the same source

From: Orphanet

Additional reported features include Abnormality of temperature regulation (Frequent (79-30%)); Hepatomegaly (Frequent (79-30%)); Hypogonadotropic hypogonadism (Frequent (79-30%)); Irritability (Frequent (79-30%)); Muscle weakness (Frequent (79-30%)); Reduced bone mineral density (Frequent (79-30%)); Respiratory insufficiency (Frequent (79-30%)); Cholelithiasis (Occasional (29-5%)); Hepatitis (Occasional (29-5%)); Hypertrophic cardiomyopathy (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Beta thalassemia is Haematology, with a haematologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which blood-cell, marrow, bleeding or clotting finding matters most?
• Does the diagnosis need confirmation or a more precise subtype?
• Which symptoms or laboratory changes should trigger earlier review?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Beta thalassemia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.