Beta-thalassemia - causes, symptoms, diagnosis, treatment, pathology

Summary

Beta thalassemia is an autosomal recessive genetic disorder characterized by a deficiency in the production of beta-globin chains of hemoglobin, which are crucial for oxygen transport in red blood cells (RBCs). It predominantly affects populations from Mediterranean, African, and Southeast Asian regions. The disorder can be classified into three types: minor, intermedia, and major, with varying degrees of severity and symptoms. Symptoms include anemia, jaundice, hepatosplenomegaly, and growth retardation, while severe cases can lead to secondary hemochromatosis. Diagnosis is typically made through blood tests, peripheral blood smear, and hemoglobin electrophoresis. Treatment may involve blood transfusions and iron chelation therapy to manage iron overload. Regular transfusions are required for transfusion-dependent patients, while non-transfusion-dependent cases may not need them. The condition is caused by mutations in the beta-globin gene on chromosome 11, leading to reduced or absent beta-globin chain synthesis.

Takeaways

• 🩸 Beta thalassemia is a genetic disorder affecting the production of beta-globin chains in hemoglobin, leading to various forms of the disease.
• 🌍 It is most commonly seen in Mediterranean, African, and Southeast Asian populations.
• 🧬 Hemoglobin is composed of four globin chains, with different types (alpha, beta, gamma, delta) combining to form various hemoglobins like HbF, HbA, and HbA2.
• 🧬🧬 Beta-thalassemia results from a point mutation in the beta-globin gene on chromosome 11, affecting mRNA reading and beta globin synthesis.
• 👪 It is an autosomal recessive disease, requiring two mutated copies of the gene to manifest fully.
• 📉 Beta-thalassemia minor is often asymptomatic, while major requires two beta zero mutations, leading to no beta-globin chain production.
• 🚫 The deficiency causes free alpha chains to accumulate and damage red blood cells, leading to hemolysis and anemia.
• 🤒 Symptoms of beta-thalassemia major include anemia, jaundice, hepatosplenomegaly, and growth retardation.
• 🩺 Diagnosis typically starts with a blood test showing low hemoglobin, decreased MCV, and high RDW, followed by hemoglobin electrophoresis.
• 💉 Treatment may involve blood transfusions for severe cases, with iron chelation therapy to manage iron overload from transfusions.
• ⚠️ Complications of untreated or poorly managed beta-thalassemia include hemochromatosis, arrhythmias, and organ damage.
• 🧵 The hair-on-end appearance on a skull X-ray and chipmunk facies are characteristic physical findings in beta-thalassemia major.

Q & A

What is beta thalassemia?

Beta thalassemia is a genetic disorder characterized by a deficiency in the production of beta-globin chains of hemoglobin, which are the oxygen-carrying proteins in red blood cells.

Which populations are most commonly affected by beta thalassemia?

Beta thalassemia is most commonly seen in Mediterranean, African, and Southeast Asian populations.

What are the four major globin chain types that make up hemoglobin?

The four major globin chain types are alpha, beta, gamma, and delta.

What is the composition of hemoglobin A (HbA), the major adult form of hemoglobin?

Hemoglobin A is composed of two alpha globin chains and two beta-globin chains.

What is the genetic cause of beta thalassemia?

Beta thalassemia is caused by a point mutation in the beta-globin gene present on chromosome 11, which results in a partial or complete deficiency of beta globin chain production.

How is beta thalassemia inherited?

Beta thalassemia is an autosomal recessive disease, meaning two mutated copies of the gene, one from each parent, are needed to develop the disease.

What are the three types of beta thalassemia?

The three types of beta thalassemia are minor, intermedia, and major, which differ in the severity of symptoms and the level of beta-globin chain synthesis.

What is the consequence of free alpha chains accumulating within red blood cells in beta thalassemia?

The accumulation of free alpha chains within red blood cells leads to the formation of intracellular inclusions that damage the red blood cell membrane, causing hemolysis.

What are the common symptoms of beta thalassemia major in infants?

Common symptoms of beta thalassemia major in infants include anemia-like symptoms such as pallor, shortness of breath, easy fatigue, jaundice, hepatosplenomegaly, and growth retardation.

How is the diagnosis of beta thalassemia typically confirmed?

The diagnosis of beta thalassemia is typically confirmed with hemoglobin electrophoresis, which shows low amounts of HbA, but an increase in HbF and HbA2 levels.

What are the two clinically relevant categories of beta thalassemia based on the need for blood transfusions?

The two clinically relevant categories are transfusion-dependent thalassemia, which includes phenotypes requiring recurrent blood transfusions, and non-transfusion-dependent thalassemia, which includes milder cases that do not require regular blood transfusions.

How can iron overload from regular blood transfusions be managed in beta thalassemia patients?

Iron overload from regular blood transfusions can be managed using iron chelating agents like deferoxamine, which help to remove excess iron through feces or urine.