Hemoglobinopathies And Thalassemias Flashcards
Alpha Hb genes
. On chromosome 16
. 2 zeta genes for alpha chains
. Contains gene expressed in early development as an alpha-globin like component of embryonic Hb
Beta Hb genes
. Chromosome 11
. Contains epsilon gene expressed in early embryonic development
. 2 gamma gene expression seen in Hb F
. Delta gene for globin chain found in adult HbA2
Steps in globin chain synthesis
. Starts in nucleus of blood cell precursors where it’s transcribed
. mRNA produced, 2 introns removed and 2 Econ’s join
. Mature mRNA is translated producing globin chain
Hb A
. Contain the alpha and beta tetramer structure
. HbA2 synthesized in low levels
Hb F
. Tetramer of 2 alpha and 2 gamma chains
Hb synthesis timeline
. 1 month after conception synthesis starts in yolk sac
. After 5th week the Hb synthesis switches to liver then the marrow w/ product Hb F
. Last months Hb F is 60% of rbcs
. Hb A starts in bone marrow at 8th month and gradually replaces Hb F
2,3-BPG binding to Hb F
. Weakly binds so f has higher O2 affinity than A
Why does Hb F need higher O2 affinity?
To facilitate transfer from maternal circulation across placenta to RBC of fetus
Hb A2
. Minor component of normal adult Hb that appears shortly after birth and eventually constitutes 2% total Hb
HbA1c
. HbA undergoes glycation
. Glycation dependent on [glucose] in blood plasma
. Inc. amounts found in diabetic patients
. Gives indication of blood glucose level over 120 days (RBC life span)
Glycation
NONENZYMATIC addition of glucose to HbA
Hemoglobinopathies
. Result from production of Hb w/ altered amino acid sequence
Hb S disease
. Sickle cell
. Single point mutation in gene (Val instead of Glu at position 6) for beta-globin making it beta-s
. Mutation makes HbS less negative than HbA
. Autosomal recessive gene
Sickle cell prevalence
. 50,000 Mexicans affects
. 1:500 black children
. 1/12 black people heterozygous carriers
SIckle cell characteristics
. Infant don’t show symptoms until Hb F is replaced by HbS
. Lifelong episodes of pain, chronic hemolytic anemia, inc. bilirubin, and inc. suspectibility to infection
. Lifespan of RBC w/ HbS is less than 20 days
. Cell looks sickled