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Hematology: RBC Thalassemia: Chromosome 16: Alpha Gene and Zeta Gene Chromosome 11: Beta Gene, Delta Gene, Gamma

This document summarizes thalassemia, a genetic blood disorder caused by abnormalities in globin chain synthesis. There are two main types: alpha-thalassemia resulting from reduced or absent alpha globin production, and beta-thalassemia with reduced beta globin. Symptoms are usually mild until ages 6-24 months when fetal hemoglobin is replaced, causing anemia. Diagnosis involves blood tests showing microcytic hypochromic cells and abnormalities in hemoglobin electrophoresis or HPLC.

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Romie Solacito
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135 views3 pages

Hematology: RBC Thalassemia: Chromosome 16: Alpha Gene and Zeta Gene Chromosome 11: Beta Gene, Delta Gene, Gamma

This document summarizes thalassemia, a genetic blood disorder caused by abnormalities in globin chain synthesis. There are two main types: alpha-thalassemia resulting from reduced or absent alpha globin production, and beta-thalassemia with reduced beta globin. Symptoms are usually mild until ages 6-24 months when fetal hemoglobin is replaced, causing anemia. Diagnosis involves blood tests showing microcytic hypochromic cells and abnormalities in hemoglobin electrophoresis or HPLC.

Uploaded by

Romie Solacito
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as DOCX, PDF, TXT or read online on Scribd
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HEMATOLOGY: RBC THALASSEMIA

Romie Solacito, MLS4C


Globin Synthesis Abnormalities
 Thalassemia – quantitative abnormalities
 Hemoglobinopathies – qualitative abnormalities
o Defects on the Amino Acid present:
Amino Acid Substitution and Amino Acid
Elongation

Genetics of Globin Synthesis


 Chromosome 16: Alpha gene and Zeta gene
 Chromosome 11: Beta gene, Delta gene, Gamma
gene, and Epsilon gene

Six Normal Hemoglobin


 Embryonic Hemoglobin:
o Gower 1 – Zeta and Epsilon
o Gower 2 – Alpha and Epsilon
o Portland – Zeta and Gamma
 Fetal Hemoglobin:
o Hemoglobin F – Alpha and Gamma
 Adult Hemoglobin  1st 2 months of gestation – Gower 1 (zeta &
o A1 – Alpha and Beta epsilon)
o A2 – Alpha and Delta  2nd month of gestation – Gower 2 (alpha and
epsilon); High Portland (zeta and gamma)
Development Expression
 10 weeks of gestation – switching (zeta to alpha)  Deletion of one or more globin chains
at C16; switching (epsilon to gamma) at C11;
formation of Hemoglobin F (alpha and gamma) Pathophysiology
 Throughout Fetal Life – Hemoglobin F  Reduced or absent production of a particular
 Shortly After Birth – DOWN regulation of gamma globin chain with reduced hemoglobin synthesis
chain; UP regulation of beta chain; Hemoglobin  Unequal production of the alpha or beta chain
A (alpha and beta)
 6 months of Adulthood – Hemoglobin A1 (alpha Beta-Thalassemia Mechanism
and beta); low amount of A2 (alpha and delta)  Asymptomatic till 6 months due to increase
Hemoglobin F
Thalassemia: Genetic Defects  Symptoms appear between 6 to 24 months after
 Reduced or absent transcription of mRNA the compensation of gamma to beta switching
o Decreased RNA stability  Increased Erythropoietin but still exhibits
 mRNA processing error ineffective erythropoiesis; promotes Bone
o results to no globin chain or altered Marrow Expansion
globin chain production  Increased Iron accumulation: increased
 Translation error Erythropoietin = decreased hepcidin
o Frameshift Mutation  Progressed to reduction of bone mineral
o Missense Mutation thinning
o Nonsense Mutations o Increased risk of pathologic fractures
o Exhibit frontal bossing PARAMETERS THALASSEMIA IRON DEFICIENCY
Blood Picture Micro, Hypo Micro, Hypo
Alpha-Thalassemia Mechanism Serum Ferritin ^/N v
 Decreased production of alpha chain Serum Iron N v
 Leads to the formation of excess gamma chain: TIBC v/N ^
Hemoglobin Barts (four gamma) from Transferrin v/N ^
Hemoglobin F
 After 6 months gamma switches to beta chain:
Hemoglobin H (four beta) from Hemoglobin A
 Hemoglobin Bart and Hemoglobin H
o Increased affinity to oxygen
o Causes marked hypoxia leading to
cardiac failure and Hydrops Fetalis
GENOTYPE DISORDER
--/-- Barts Hydrops Fetalis/α Thalassemia
Major
--/-α Hemoglobin H Disease
--/αα α Thalassemia Minor
α-/α- α Thalassemia Minor
αα/α- Silent Carrier
αα/αα None

Laboratory Diagnosis
 CBC with peripheral blood film: Microcytic,
Hypochromic
 Hematocrit: decreased (<35%)
 Hemoglobin: decreased (<12g/dL)
 RDW: increased (>14.5%)
 Electrophoresis:
o Cellulose Acetate – pH 8.4 to 8.6
 CSFA
o Citrate Agar – pH 6.0 to 6.4
 CSAF
 Cation-exchange HPLC
 Capillary Zone Electrophoresis
 Alkaline Denaturation Test
 Kleihauer – Betke Test
 Molecular Testing: Polymerase Chain Reaction

Fast Moving: Hemoglobin Bart and Hemoglobin H

CATHODE ANODE
C, G, E, As > S, G, D, Leopre > F > A > Portland > Barts > H

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