Thalassemias - Pediatric - Lecture Slides, Slides of Pediatrics

Download Thalassemias - Pediatric - Lecture Slides and more Slides Pediatrics in PDF only on Docsity!

The Thalassemias

Introduction

• Heritable, hypochromic anemias-varying

degrees of severity

• Genetic defects result in decreased or absent

production of mRNA and globin chain

synthesis

• At least 100 distinct mutations
• High incidence in Asia, Africa, Mideast, and

Mediterrenean countries

Globin Chains

• Alpha Globin
  • 141 amino acids
  • Coded for on Chromosome 16
  • Found in normal adult hemoglobin, A1 and A
• Beta Globin
  • 146 amino acids
  • Coded for on Chromosome 11, found in Hgb A
• Delta Globin
  • Found in Hemoglobin A2--small amounts in all adults
• Gamma Globin
  • Found in Fetal Hemoglobin
• Zeta Globin
  • Found in embryonic hemoglobin

Genetics

• Alpha globins are coded on chromosome 16
  • Two genes on each chromosome
  • Four genes in each diploid cell
  • Gene deletions result in Alpha-Thalassemias
• Also on chromosome 16 are Zeta globin genes— Gower’s hemoglobin (embryonic)
• Beta globins are coded on chromosome 11
  • One gene on each chromosome
  • Two genes in each diploid cell
  • Point mutations result in Beta-Thalassemias
• Also on chromosome 11 are Delta (Hgb A2) and Gamma (Hgb F) and Epsilon (Embryonic)

Alpha Thalassemias

• Usually no treatment indicated
• 4 deletions incompatible with life
• 3 or fewer deletions have only mild anemia

Beta Thalassemias

• Result from Point Mutations on genes
• Severity depends on where the hit(s) lie

b^0 -no b-globin synthesis; b+^ reduced synthesis

• Disease results in an overproduction of a-

globin chains, which precipitate in the cells

and cause splenic sequestration of RBCs

• Erythropoiesis increases, sometimes

becomes extramedullary

Beta Thalassemia Major

• Reduced or nonexistent production of b-globin
  • Poor oxygen-carrying capacity of RBCs
    • Failure to thrive, poor brain development
  • Increased alpha globin production and precipitation
    • RBC precursors are destroyed within the marrow
• Increased splenic destruction of dysfunctional RBCs
  • Anemia, jaundice, splenomegaly
• Hyperplastic Bone Marrow
  • Ineffective erythropoiesis—RBC precursors destroyed
    • Poor bone growth, frontal bossing, bone pain
  • Increase in extramedullary erythropoiesis
• Iron overload—increased absorption and transfusions
  • Endocrine disorders, Cardiomyopathy, Liver failure

b-Thalassemia Major—Lab findings

• Hypochromic, microcytic anemia
  • Target Cells, nucleated RBCs, anisocytosis
• Reticulocytosis
• Hemoglobin electrophoresis shows
  • Increased Hgb A2—delta globin production
  • Increased Hgb F—gamma globin production
• Hyperbilirubinemia
• LFT abnormalities (late finding)
• TFT abnormalities, hyperglycemia (late

endocrine findings)

b-Thalassemia Major

Complications and Emergencies

• Sepsis—Encapsulated organisms
  • Strep Pneumo
• Cardiomyopathy—presentation in CHF
  • Use diuretics, digoxin, and deferoxamine
• Endocrinopathies—presentation in DKA
  • Take care during hydration so as not to precipitate CHF from fluid overload

Anticipatory Guidance and Follow Up

• Immunizations—Hepatitis B, Pneumovax
• Follow for signs of diabetes, hypothyroid,

gonadotropin deficiency

• Follow for signs of cardiomyopathy or CHF
• Follow for signs of hepatic dysfunction
• Osteoporosis prevention
  • Diet, exercise
  • Hormone supplementation
  • Osteoclast-inhibiting medications
• Follow ferritin levels