Hemoglobinopathies Flashcards
This disease is diagnosable during the 2nd half of first year of life
Sickle Cell Anemia
What are the adult tetramers of Hb.
Hb alpha2, beta2, Hb delta2, alpha2
Fetal Hb tetramers
Hb gamma2, alpha2
Hb Portland tetramers
Hb gamma2, zeta2
HbS amino acid switch
Glu»»Val at 6th A.A.
HbS tetramers
Hb alpha2, BetaS2
Symptoms of HbSS in order to diagnose
palor, failure to thrive, repeated infections, splenomegaly
Painful Episode of HbSS symptoms
infarction of tissue, backup of RBCs in spleen, severe anemia
Chronic Painful Episodes of HbSS lead to
chronic infections, organ malfunction, pigmented gallstones, increased fetal mortality in mothers with HbSS
What state of Hb will HbSS sickle in?
T state (relaxed state)
What advantage do individuals with HbSA have?
heterozygote advantage, lower malaria risk
Beta-Thalesseamia results from
single base substitution, large deletions, insertions
initial presentation of Beta-Thal
severe hemolytic anemia, many reticulocytes, microcytic, hypochromatic
what age is Beta-Thal diagnoasble
around 2 years of age
Progression of Beta-Thal Major untreated
growth retardation, genu valgum, jaundice, hepatosplenomegaly, “chipmunk-face”
Treatment for Beta-Thal Major
Blood Transfusions and chelation therapy
Why chelation therapy given to patient for Beta-Thal?
iron overloading, patient must watch ferritin levels
Drugs used for Tx of Beta-Thal Major
Desferrioxamine (IV-subcu)
oral Deferasirox
What is the cure for Beta-Thal?
Bone marrow transplant
Cause of Beta-Thal intermedia
reduced beta Hb less than 50% of normal
Symptoms associated with beta-Thal Intermedia
splenomegaly, gall stones, iron overload, variable anemia
Does a patient with beta-thal intermedia require routine blood transfusions
No
Beta-Thal minor
production of Hb-beta is above 50% of normal
Treatment for Beta-thal minor
asymptotic no treatment-mild microcytic, hypo chromatic anemia
Genetics of beta-thal major
Hb beta0, beta0 or Hb beta+, beta0
Genetics of beta-thal intermedia
Hb beta+, beta+
In beta-thal disease will there be a production of homo-tetramers?
no, lack of beta surplus of alpha
In beta-thal, will there be precipitate of alpha ?
yes
Alpha-Thalassemia 1
Allele B , Asians
Alpha-Thal 2
Allele A, Africans and Asians
What chromosome is altered for alpha-thal?
chromosome 16
Silent Carrier of alpha-thal
deletion of beta 2
Alpha-Thal trait
deletion of beta 2, alpha 2
beta 1, beta 2
Hb H disease
everything deleted except alpha 1
Hb Barth’s disease
Everything deleted
Hb H disease genetics and what is present at the baby’s birth in Hb H disease
Hb beta 4 protein and barths protein (Hb-gamma 4)
Hb Barth’s protein is main type present in
Hb Portland (Hb zeta2, gamma 2)
Will you from homo-tetramers in Hb H disease
yes, beta 4 and gamma Hb chains (completed absence of alpha chains)
HbE and HbC have changes made on what allele
beta allele
HbE changes from what to what (genetics)
on 26th A.A, Glu»»Lys
Hb AE will provide some protection against
P. falciparum malaria
Beta-Thal/HbS will present with what symptoms
Symptoms of Sickle Cell disease
