HBA1

Hemoglobin A1 (HBA1), also known as HbA1 or α2β2, is a type of hemoglobin found in red blood cells responsible for transporting oxygen from the lungs to tissues.  It is the predominant form of hemoglobin in adults, comprising 95–98% of the total hemoglobin. 

HBA1 contains two alpha and two beta chains, distinguishing it from other forms of hemoglobin such as hemoglobin A2 and hemoglobin F, which is the main form in fetuses.

Mutations or deletions in the HBA1 gene can lead to alpha-thalassemia, a condition characterized by reduced or absent production of alpha-globin chains.  This can result in various forms of alpha-thalassemia, ranging from mild, asymptomatic carrier states to severe forms such as HbH disease and Hb Bart's hydrops fetalis syndrome. 

Unlike HbA1c, which is a glycated form of hemoglobin used to monitor long-term blood sugar levels and manage diabetes, HBA1 mutations primarily affect hemoglobin structure and function, leading to hematological disorders.

Understanding HBA1: What is HBA1?  [2., 3.] 

The HBA1 Protein

Hemoglobin A1 is one type of hemoglobin found in red blood cells that transport oxygen from the lungs to tissues.  Hemoglobin A1 is also known as hemoglobin A (HbA) or α2β2. 

It is the most common type of hemoglobin in adults, making up 95–98% of hemoglobin.  It contains two alpha and two beta chains.

In addition to HBA1, there are other forms of hemoglobin including hemoglobin A2, and hemoglobin F, the dominant form of hemoglobin found in fetuses.  

Two other forms of hemoglobin are associated with disease states: hemoglobin Type S (HgbS)

is associated with sickle cell anemia, a severe form of sickle cell disease. 

Hemoglobin Type C (HgbC) is linked to hemolytic anemia, a condition where red blood cells are destroyed more rapidly than normal, resulting in a shorter lifespan for these cells.  Hemoglobin S and hemoglobin C predominantly affect individuals of African descent.

HBA1 is a form of hemoglobin that binds to glucose in the blood, and its levels are used to measure long-term blood sugar control. 

The most commonly referenced type within this group is HbA1c (hemoglobin A1c), which reflects the average blood glucose levels over the past two to three months.  Elevated HbA1c levels indicate poor blood sugar control and are commonly used to diagnose and manage diabetes. 

High levels of HbA1c can also point to potential complications in diabetes, such as damage to the liver and kidneys, highlighting its importance as a biomarker for long-term glycemic management.

The HBA1 Gene  [2.] 

Hemoglobin A1 (HBA1) is one of the genes that control the expression of the alpha subunit of the hemoglobin protein.  Defects in HBA1 can lead to decreased alpha chain production and therefore abnormal hemoglobin production, resulting in conditions known as hemoglobinopathies. 

These can manifest in three primary ways: structural defects in the hemoglobin molecule, diminished production of the hemoglobin subunit (thalassemias), and abnormal associations of otherwise normal subunits. 

Structural defects involve mutations in the gene that change a single amino acid, which can sometimes cause significant disturbances in hemoglobin function, as seen in diseases like sickle cell anemia. 

Thalassemias, including alpha thalassemia, occur when there is reduced production of one of the hemoglobin subunits, leading to an imbalance that damages red blood cells and causes anemia. 

Severe alpha thalassemia can lead to the formation of beta-globin tetramers, which are functionally inactive and do not transport oxygen. 

HBA1 and Alpha-Thalassemia  [1., 4., 5.] 

Mutations or deletions in the HBA1 and/or HBA2 genes can lead to reduced or absent production of alpha-globin, resulting in the different forms of alpha-thalassemia.  

The number of affected HBA1 and HBA2 gene copies determines the specific type and severity of alpha-thalassemia:

• Loss or alteration of all four alpha-globin gene copies (two HBA1 and two HBA2) results in Hb Bart hydrops fetalis syndrome, the most severe form

• Loss or alteration of three alpha-globin gene copies causes HbH disease, a moderate to severe form

• Loss of two alpha-globin gene copies leads to alpha-thalassemia trait, a milder form

• Loss of one alpha-globin gene copy results in an asymptomatic alpha-thalassemia carrier state 

Symptoms vary based on the type, from no symptoms (silent carrier) to life-threatening anemia (Hb Bart syndrome).

Common symptoms include fatigue, weakness, shortness of breath, pale skin, jaundice, enlarged spleen, and failure to thrive in infants.

Carriers of alpha-thalassemia typically exhibit reduced MCV and MCH, distinguishing them from beta-thalassemia carriers.  [4.]

Severe forms like HbH disease and Hb Bart syndrome can lead to serious complications such as heart defects, abnormal bone growth, iron overload, and organ damage if not properly managed.

Diagnosis is based on blood tests like complete blood count, hemoglobin electrophoresis, and genetic testing to identify mutations.

Treatment depends on severity, ranging from no treatment needed (silent carrier) to regular blood transfusions, iron chelation therapy, bone marrow transplant, or intrauterine transfusions for the most severe forms.

Genetic Alterations in the HBA1 Gene

The gene for the HBA1 protein may contain alterations or mutations that cause alterations of function of the HBA1 protein.  

Testing for genetic alterations in the form of SNPs is increasingly available and can shed light on an individual’s potential for health and disease.  

What is a SNP?

A SNP, or single nucleotide polymorphism, refers to a variation at a single position in a gene along its DNA sequence.  A gene encodes a protein, so an alteration in that gene programs the production of an altered protein.  

As a type of protein with great functionality in human health, alterations in genes for enzymes may confer a difference in function of that enzyme.  The function of that enzyme may be increased or decreased, depending on the altered protein produced.  

SNPs are the most common type of genetic variation in humans and can occur throughout the genome, influencing traits, susceptibility to diseases, and response to medications.

The completion of the Human Genome Project has significantly expanded opportunities for genetic testing by providing a comprehensive map of the human genome that facilitates the identification of genetic variations associated with various health conditions, including identifying SNPs that may cause alterations in protein structure and function.  

Genetic testing for SNPs enables the identification of alterations in genes, shedding light on their implications in health and disease susceptibility.

Laboratory Testing for HBA1 

Test Information 

Standard hemoglobin testing is performed as part of routine blood work called a complete blood count, or CBC.  It determines the amount of hemoglobin present in the blood but not the type. 

HBA1 testing may be done to assess the amount and structure of HBA1 present in the bloodstream, typically to determine whether an individual has a hematological condition such as sickle cell anemia or a thalassemia.  

HBA1 testing for the amount and structure of the HBA1 hemoglobin complex present in the bloodstream is generally done through a process called electrophoresis.   

Alternatively, the HBA1 gene may be tested to determine whether the individual is a carrier that could put them at risk for a thalassemia or another condition.   

Genetic testing for single nucleotide polymorphisms (SNPs) typically involves obtaining a sample of DNA which can be extracted from blood, saliva, or cheek swabs. 

The sample may be taken in a lab, in the case of a blood sample.  Alternatively, a saliva or cheek swab sample may be taken from the comfort of home. 

Test Preparation

Blood tests for HBA1 typically do not require special preparation, although it is essential to consult the ordering provider prior to sample collection.

Prior to undergoing genetic testing, it's important to consult with a healthcare provider or genetic counselor to understand the purpose, potential outcomes, and implications of the test.  This consultation may involve discussing medical history, family history, and any specific concerns or questions. 

Additionally, individuals may be advised to refrain from eating, drinking, or chewing gum for a short period before providing a sample to ensure the accuracy of the test results.  Following sample collection, the DNA is processed in a laboratory where it undergoes analysis to identify specific genetic variations or SNPs. 

Once the testing is complete, individuals will typically receive their results along with interpretation and recommendations from a healthcare professional. 

It's crucial to approach genetic testing with proper understanding and consideration of its implications for one's health and well-being.

Interpreting the HBA1 Test

Whether a blood test to assess the type of hemoglobin was ordered, or genetic testing was performed, it is essential to consult with the ordering provider or another medical expert for proper interpretation, diagnosis and treatment.  

Patient-Centric Approaches in Genetic Testing

A patient-centered approach to SNP genetic testing emphasizes individualized medicine, tailoring healthcare decisions and interventions based on an individual's unique genetic makeup.

When that is combined with the individual’s health status and health history, preferences, and values, a truly individualized plan for care is possible. 

By integrating SNP testing into clinical practice, healthcare providers can offer personalized risk assessment, disease prevention strategies, and treatment plans that optimize patient outcomes and well-being. 

Genetic testing empowers a deeper understanding of genetic factors contributing to disease susceptibility, drug response variability, and overall health, empowering patients to actively participate in their care decisions. 

Furthermore, individualized medicine recognizes the importance of considering socioeconomic, cultural, and environmental factors alongside genetic information to deliver holistic and culturally sensitive care that aligns with patients' goals and preferences. 

Through collaborative decision-making and shared decision-making processes, patients and providers can make informed choices about SNP testing, treatment options, and lifestyle modifications, promoting patient autonomy, engagement, and satisfaction in their healthcare journey.

Genetic Panels and Combinations

Integrating multiple biomarkers into panels or combinations enhances the predictive power and clinical utility of pharmacogenomic testing.  

Biomarker panels comprising a variety of transporter proteins and enzymes including drug metabolizing enzymes offer comprehensive insights into individual drug response variability and treatment outcomes. 

Combining genetic SNP testing associated with drug transport, metabolism, and pharmacodynamics enables personalized medicine approaches tailored to individual patient characteristics and genetic profiles.

Frequently Asked Questions (FAQs) on HBA1

The FAQ section addresses common questions and concerns about HBA1, providing clear and concise answers for better understanding.  

What Is HBA1?

HBA1, also known as hemoglobin A1, is the most form of hemoglobin and the form that is typically glycated, meaning it has glucose attached to it. 

Glycated hemoglobin A1, or hemoglobin A1c, is used to measure average blood sugar levels over the past two to three months, providing an indication of long-term glucose control in the body.

What Is the HBA1 Blood Test?

The HBA1 blood test assesses the type of hemoglobin present in the blood to diagnose or rule out potentially troubling hematologic conditions such as sickle cell anemia or certain thalassemias.  

It should not be confused with the HbA1c blood test or glycated hemoglobin test, which measures the percentage of hemoglobin in the blood that is glycated. This test is commonly used to diagnose and monitor diabetes by reflecting average blood glucose levels over a period of time.

What Is the HBA1 Normal Range?

A normal test result for HBA1 does not show alterations in the HBA1 protein.  

In contrast, the HbA1c, or A1C,  test for glycated hemoglobin is typically between 4% and 5.6%. Levels of the HbA1c test between 5.7% and 6.4% indicate prediabetes, while levels of 6.5% or higher suggest diabetes. 

How Is the HBA1 Test Performed?

The HBA1 test is a simple blood test usually performed in a laboratory or healthcare provider's office. A blood sample is taken from a vein in your arm, and the sample is then analyzed to determine the type of hemoglobin present.  

A genetic test can be done with a blood, cheek swab or saliva sample.

Why Is the HBA1 Test Important?

The HBA1 test is important for individuals with a family history or symptoms of major hemoglobinopathies such as sickle cell anemia or a thalassemia.  

In contrast, the HbA1c test is crucial for managing diabetes because it provides a long-term overview of blood glucose control.  

Unlike daily blood sugar tests that show immediate levels, the HBA1 test reflects average blood sugar levels over several months, helping healthcare providers assess the effectiveness of treatment plans and make necessary adjustments.

How Often Should I Have an HBA1 Test?

Individuals at risk for serious hemoglobinopathies such as sickle cell anemia or a thalassemia will likely only need to have their HBA1 test run once.

In contrast, the HbA1c test needs to be run roughly every 3-6 months in patients with dysglycemia.  

For individuals with diabetes, it is generally recommended to have an HBA1 test at least twice a year.  However, your healthcare provider may suggest more frequent testing, such as every three months, if your blood sugar levels are not well-controlled or if changes to your treatment plan are being made.

What Factors Can Affect HBA1 Levels?

HBA1 levels are typically determined genetically,  However, glycated HBA1, or HbA1c levels, are heavily reliant on several diet and lifestyle factors as well as an individual’s medical history.  

Several factors can influence HBA1 levels including blood sugar levels, certain medical conditions (such as anemia or kidney disease), and lifestyle factors (such as diet and exercise). 

It is important to discuss any unusual results with your healthcare provider to determine the cause and appropriate action.

Can the HBA1 Test Diagnose Diabetes?

While the HBA1 genetic or electrophoresis test is used to diagnose serious hemoglobinopathies, the HbA1c test is commonly used to diagnose diabetes and prediabetes. 

An HBA1 level of 6.5% or higher typically indicates diabetes, while a level between 5.7% and 6.4% suggests prediabetes. 

Diagnosis should always be confirmed by a healthcare provider through additional testing and evaluation.

What Should I Do if My HBA1 Levels Are High?

This question is typically asked in reference to an individual’s HbA1c.  

If your HbA1c levels are high, it is important to work with your healthcare provider to develop a management plan.  This may include lifestyle changes such as diet and exercise, medication adjustments, and regular monitoring of blood glucose levels. 

High HBA1c levels indicate that blood sugar is not well-controlled, which can increase the risk of diabetes complications.

Are There Any Risks Associated with the HBA1 Test?

The HBA1 test is a low-risk procedure. The most common risk is slight discomfort or bruising at the site where blood is drawn. 

Genetic testing may require a cheek swab or salivary sample, which is also a low-risk procedure.

Serious complications are rare, and the test provides valuable information.

Order Testing for Blood Sugar Assessment

Click here to compare tests and order testing for blood sugar levels.  

Order Genetic Testing

Click here to compare genetic test panels and order genetic testing for health-related SNPs.