Microcytic Anemias: Beta-thalassemia

Questions and Answers

What is the clinical outcome of Beta-thalassemia Major?

Severe microcytic anemia with target cells and increased anisopoikilocytosis requiring blood transfusions.

What mutation results in beta-thalassemia?

Inversion on chromosome 2

Point mutation in splice sites (correct)

Deletion of the ß-globin gene

Translocation of chromosome 11

What symptoms are associated with lead poisoning?

Lead lines on gingivae, encephalopathy, abdominal colic, and drop-wrist.

Which of the following factors can lead to sideroblastic anemia?

All of the above Signup and view all the answers

Lead inhibits heme synthesis.

True Signup and view all the answers

What treatment is used for lead poisoning?

Chelation with succimer, EDTA, and dimercaprol. Signup and view all the answers

The presence of ______ can be observed in the bone marrow of patients with sideroblastic anemia.

ringed sideroblasts Signup and view all the answers

What are the lab findings associated with sideroblastic anemia?

Increased iron, normal/increased TIBC, increased ferritin, and ringed sideroblasts. Signup and view all the answers

Study Notes

Beta-thalassemia

Caused by point mutations on chromosome 11 affecting ß-globin synthesis.
Commonly found in individuals of Mediterranean descent.
Beta-thalassemia Minor: Mutation of 1 gene leads to mild microcytic anemia and increased HbA₂.
Beta-Thalassemia Intermedia: Mutation of 2 genes (ß+/B+ or ß+/ßº) results in variable anemia severity, from mild to transfusion-dependent.
Beta-thalassemia Major: Mutation of 2 genes leads to severe microcytic anemia, requiring blood transfusions. Symptoms include target cells, anisopoikilocytosis, secondary hemochromatosis, marrow expansion ("crew cut" skull x-ray), splenomegaly, hepatomegaly, risk of parvovirus B19-induced aplastic crisis, increased HbF and HbA₂.
Sickle Cell Beta-Thalassemia: Occurs with 1 gene mutated (ß+/HbS or Bº/HbS), leading to mild to moderate sickle cell disease based on the presence or absence of ß-globin synthesis.

Lead Poisoning

Lead inhibits ferrochelatase and ALA dehydratase, reducing heme synthesis and increasing RBC protoporphyrin.
Inhibits rRNA degradation, causing RBCs to retain aggregates of rRNA, observed as basophilic stippling.
Symptoms include:
- Burton lines on gingivae and long bone metaphyses on x-ray.
- Encephalopathy.
- Abdominal colic and sideroblastic anemia.
- Neurological symptoms such as drop-wrist and foot drop.
Treatment involves chelation therapy using succimer, EDTA, or dimercaprol.
Increased exposure risk in pre-1978 homes with chipped paint and occupational settings.

Sideroblastic Anemia

Causes can be genetic (X-linked ALA synthase defect), acquired (myelodysplastic syndromes), or reversible (alcohol, lead poisoning, vitamin B6 deficiency, copper deficiency, certain drugs like isoniazid and linezolid).
Lab findings include:
- Increased iron levels.
- Normal or increased Total Iron Binding Capacity (TIBC).
- Increased ferritin levels.
- Presence of ringed sideroblasts in bone marrow with iron-laden mitochondria.
Peripheral blood smear may show basophilic stippling of RBCs.
Some acquired variants might present as normocytic or macrocytic anemias.
Treatment includes pyridoxine (Vitamin B6), which acts as a cofactor for ALA synthase.

Description

This quiz explores the genetic causes and clinical implications of Beta-thalassemia, a type of microcytic, hypochromic anemia. It examines the mutations affecting ß-globin synthesis and the prevalence of this disorder among various populations, particularly those of Mediterranean descent.