Inheritance of Beta-Thalassemia: Consultation, Diagnosis & Treatment

Inheritance of Beta-Thalassemia: Consultation, Diagnosis & Treatment

Beta-Thalassemia is one of the most common genetic blood disorders worldwide. It is an autosomal recessive disorder, meaning the disease is inherited when both parents carry and pass on the defective gene.

Thalassemia is broadly classified into:

• Alpha Thalassemia – caused by deletions in the alpha-globin genes (HBA1 and HBA2) on chromosome 16.

• Beta Thalassemia – caused by mutations in the HBB gene on chromosome 11, which reduces (β⁺) or completely stops (β⁰) the production of beta-globin chains.

When beta-globin synthesis is impaired, hemoglobin formation is defective, leading to varying degrees of anemia.

Types of Beta-Thalassemia

The severity of the disease depends on the genetic mutation:

1. Beta-Thalassemia Major (β⁰/β⁰)

• Most severe form.

• No production of functional beta chains.

• Absence of Hemoglobin A.

• Patients develop severe anemia early in life and usually require lifelong blood transfusions.

2. Beta-Thalassemia Intermedia (β⁺/β⁰ or β⁺/β⁺)

• Moderate severity.

• Some Hemoglobin A is produced.

• Symptoms vary; may or may not require regular transfusions.

3. Beta-Thalassemia Minor (β/β⁰ or β/β⁺)

• Carrier state (one mutated gene, one normal gene).

• Usually asymptomatic or mild anemia.

• Carriers may unknowingly pass the mutation to children.

👉 This is why genetic consultation and carrier screening are crucial for couples planning a family.

Importance of Genetic Counseling

• Accurate Diagnosis – Differentiating between minor, intermediate, and major thalassemia.

• Recurrence Risk Calculation – Understanding the chances of passing the disorder to children.

• Prenatal Testing – Early identification of thalassemia in the fetus to guide clinical decisions.

At LABASSURE, we provide comprehensive genetic counseling for thalassemia carriers and affected families.

Diagnosis of Beta-Thalassemia

Beta-thalassemia can be diagnosed through:

1. Haematological Testing

• Complete Blood Count (CBC) – measurement of red blood cells (RBCs).

• Peripheral Blood Smear – identifies abnormal RBC morphology.

2. Molecular Genetic Testing

• Targeted Mutation Analysis – Detects common genetic defects using ARMS PCR, real-time PCR, or microarray technology.

• Rare Mutation Detection – Involves PCR and DNA sequencing of the HBB gene coding region and flanking sequences. Sensitivity is >99%.

Common Beta-Thalassemia Mutations in India

Research has identified several frequent mutations in the Indian population:

• 619bp deletion (g.63201_63819del619)

• IVS1-5G>C (c.92+5G>C)

• IVS1-1G>T (c.92+1G>T)

• Fr41-42 (c.124_127delTTCTI)

• Fr8-9 (c.27_28insG)

Rare mutations reported in India include:

• Cap+1 (A>T)

• Codon 15 (G>A / -T)

• Codon 5 (-CT)

• Codon 16 (-C)

• Codon 26 (G>A)

• Codon 30 (G>C)

• Codon 41 (-C)

(Source: Arora et al., 2001; Saxena et al., 1998)

Treatment & Management of Beta-Thalassemia

The treatment depends on the type and severity:

• Beta-Thalassemia Major – Requires regular blood transfusions, iron chelation therapy, and in some cases, bone marrow transplantation.

• Intermedia – May need occasional transfusions and supportive care.

• Minor – Generally does not require treatment, but genetic counseling is important.

Future advancements include gene therapy and new drug-based approaches to reduce transfusion dependency.

Key Takeaways

• Beta-Thalassemia is inherited in an autosomal recessive manner.

• Carriers are often asymptomatic, making carrier screening essential.

• Genetic counseling and prenatal testing help families make informed decisions.

• LABASSURE offers advanced diagnostic solutions for accurate detection and management of thalassemia.

📧 For appointments or genetic consultation, contact us at info@labassure.com

References:

• Arora, S. et al., 2001. Prenatal diagnosis of haemoglobinopathies. Natl Med J India, 14, 340–342.

• Saxena, R. et al., 1998. Prenatal diagnosis of β-thalassaemia: experience in a developing country. Prenatal Diagnosis, 18(1): 1–7.

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