Alpha thalassemia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

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

In people with the characteristic features of alpha thalassemia, a reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications.

Two types of alpha thalassemia can cause health problems. The more severe type is known as hemoglobin Bart hydrops fetalis syndrome, which is also called Hb Bart syndrome or alpha thalassemia major. The milder form is called HbH disease.

Hb Bart syndrome is characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Additional signs and symptoms can include severe anemia, an enlarged liver and spleen (hepatosplenomegaly), heart defects, and abnormalities of the urinary system or genitalia. Without treatment, most babies with this condition are stillborn or die soon after birth because of these serious health problems. Hb Bart syndrome can also cause serious complications for women during pregnancy, including dangerously high blood pressure with swelling (preeclampsia), premature delivery, and abnormal bleeding.

HbH disease causes mild to moderate anemia, hepatosplenomegaly, and yellowing of the eyes and skin (jaundice). The features of HbH disease usually appear in early childhood, and affected individuals typically live into adulthood.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Alpha thalassemia typically results from deletions involving the HBA1 and HBA2 genes. Less commonly, changes to the DNA sequence in or near these genes cause alpha thalassemia. Such changes are often referred to as nondeletion variants. Both the HBA1 and HBA2 genes provide instructions for making a protein called alpha-globin, which is a component (subunit) of hemoglobin.

People have two copies of the HBA1 gene and two copies of the HBA2 gene in each cell. Each copy is called an allele. For each gene, one allele is inherited from a person's father, and the other is inherited from a person's mother. As a result, there are four alleles that produce alpha-globin. The different types of alpha thalassemia result from the loss or alteration of some or all of these alleles.

Deletions and nondeletion variants in one or more alleles reduce the amount of alpha-globin cells produce. Nondeletion variants tend to reduce alpha-globin more than deletions.

Hb Bart syndrome, the most severe form of alpha thalassemia, results from the loss or alteration of all four alpha-globin alleles. Such changes prevent the production of any normal alpha-globin.

HbH disease is usually caused by loss or alteration of three of the four alpha-globin alleles, which sharply reduces the amount of normal alpha-globin produced. Because nondeletion variants are usually more severe than deletions, nondeletion variants in two of the four alpha-globin alleles can result in HbH disease.

With a shortage of alpha-globin, cells make little or no normal hemoglobin. Instead, cells produce abnormal forms of hemoglobin called hemoglobin Bart (Hb Bart) or hemoglobin H (HbH). These abnormal hemoglobin molecules cannot effectively carry oxygen to the body's tissues. The substitution of Hb Bart or HbH for normal hemoglobin causes anemia and the other serious health problems associated with alpha thalassemia.

Two additional forms of alpha thalassemia are related to a reduced amount of alpha-globin. Because cells still produce some normal hemoglobin, these forms tend to cause few or no health problems. A loss of two of the four alpha-globin alleles results in alpha thalassemia trait. People with alpha thalassemia trait may have unusually small, pale red blood cells and mild anemia. A loss of one alpha-globin allele is found in alpha thalassemia silent carriers. These individuals typically have no thalassemia-related signs or symptoms.

Nondeletion variants in one or two alleles cause a range of conditions, from alpha thalassemia silent carrier to HbH disease, depending on the allele involved.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

The inheritance of alpha thalassemia is complex. Each person inherits two alpha-globin alleles from each parent. If both parents are missing at least one alpha-globin allele, their children are at risk of having Hb Bart syndrome, HbH disease, or alpha thalassemia trait. The precise risk depends on how many alleles are missing and which combination of the HBA1 and HBA2 genes is affected.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Alpha thalassemia is a fairly common blood disorder worldwide. Thousands of infants with Hb Bart syndrome and HbH disease are born each year, particularly in Southeast Asia. Alpha thalassemia also occurs frequently in people from Mediterranean countries, Africa, the Middle East, India, and Central 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.

Microcytic anemia · Very frequent (99-80%)

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

Congestive heart failure · Frequent (79-30%)

The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.

Extramedullary hematopoiesis · Frequent (79-30%)

The process of hematopoiesis occurring outside of the bone marrow (in the liver, thymus, and spleen) in the postnatal organisms.

Generalized edema · Frequent (79-30%)

Generalized abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.

Hepatosplenomegaly · Frequent (79-30%)

Simultaneous enlargement of the liver and spleen.

Pericardial effusion · Frequent (79-30%)

Accumulation of fluid within the pericardium.

Pleural effusion · Frequent (79-30%)

The presence of an excessive amount of fluid in the pleural cavity.

Other findings in the same source

From: Orphanet

Additional reported features include Reticulocytosis (Frequent (79-30%)); Abnormality of immune system physiology (Occasional (29-5%)); Anemia (Occasional (29-5%)); Anisopoikilocytosis (Occasional (29-5%)); Cholelithiasis (Occasional (29-5%)); Cognitive impairment (Occasional (29-5%)); Hemoglobin Barts (Occasional (29-5%)); Hemolytic anemia (Occasional (29-5%)); Hydrops fetalis (Occasional (29-5%)); Hyperplasia of the maxilla (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 Alpha 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

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

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.