thalassemia

1. Faculty of pharmacy-mansoura university
department of bio chemistery
thalassemia
supervisor :prof-Dr :Mamdouh el-sheshtawy
Students:
1-ebtsam hamed
2-ebthal gamal
3-abrar alaa
4-abrar labeb
5-ehsan elsheshtawy

2. Normal adult hemoglobin (HbA) consists of a
tetramer made up of two alpha-globin and two
beta-globin subunits.
The alpha globin gene is found on chromosome
16 and is duplicated, which means that each
somatic cell with its pair of homologous
chromosomes contains 4 copies of the alpha
chain gene.
The gene encoding beta globin only has two copies,
one present on each of the pair of chromosome
11.

3. Thalassemia is an inherited disease
which results when mutations affecting
the genes involved in Hb biosynthesis
lead to decreased Hb production. The
clinical phenotype results from both the
diminished amount of the particular
globin chain as well as from the
resultant chain imbalance that occurs
because of normal production of the
other globin chain.


6. Alpha
thalassemia
Beta
thalassemia
thalassemia

8. •Many mutations can affect the alpha globin gene, but the most
common
•are gene deletions
•there are 4 copies of the alpha gene in each somatic cell. Thus, phenotypes
increase in severity as the number of functional alpha genes decreases
•Silent carrier: refers to patients with one alpha gene deletion, they are
clinically asymptomatic)
•Alpha thalassemia trait: these patients have two alpha gene deletions,
and very mild phenotypes. Gene deletions can both be present on the
same chromosome, or divided between the two chromosomes which has
relevance for the patients offspring.
•Hemoglobin H disease: named reflecting the presence of the beta
tetramer HbH (B4) found in red cells. Causes moderately severe anemia.
Occurs with three alpha chain deletions
•Hydrops fetalis: the most severe form, caused by 4 alpha gene deletions
•Red cells contain gamma-globin tetramers (Hb Bart) which are ineffective
at delivering oxygen to tissues, causing anoxia, edema,
hepatosplenomegaly. Historically was not compatible with life, but
aggressive in-utero and lifelong transfusions may save individuals with
this condition

10.  mutations on chromosome 11
 hundreds of mutations possible in the beta
globin gene, therefore beta thalassemia is
more diverse
 results in excess of alpha globins

11.  Beta Thalassemia Trait
 slight lack of beta globin
 smaller red blood cells that are lighter in
colour due to lack of hemoglobin
 no major symptoms except slight anemia

12. lack of beta globin is more significant
bony deformities due to bone marrow trying to
make more blood cells to replace defective ones
causes late development, exercise intolerance,
and high levels of iron in blood due to
reabsorption in the GI tract
if unable to maintain hemoglobin levels between
6 gm/dl – 7 gm/dl, transfusion or splenectomy is
recommended

13. complete absence of beta globin
enlarged spleen, lightly coloured blood
cells
severe anemia
chronic transfusions required, in
conjunction with chelation therapy to
reduce iron (desferoxamine)

15. sign
symptom
Mechanism(s)
Shortness of
breath,
fatigue,
and weakness
(anemia)
Secondary to anemia
Deficient synthesis of the beta chain of hemoglobin causes red
cells have low HbA levels, thus explaining their phenotype and
impaired ability to transport oxygen
imbalance between alpha and beta globin production leads to a
precipitation of the relatively overabundant alpha globin cha in .
within the RBCs their precursors
Hepatomegaly Ineffective erythropoiesis leads to activation of extramedullary
erythropoiesis in areas such as the spleen, liver, lymph nodes,
and the thorax.
Hepatomegaly can result from a number of mechanisms;
extramedullary erthyropoiesis, hepatitis due to chronic
transfusion associated infections, and iron overload.

16. Bone pain
and fragility
fractures
Caused by two major mechanisms:
•Destruction of the cortex leading to weakening of the bone
•Secondary to Osteopenia/osteoporosis (mechanism above)
Cardiac
failure and
arrhythmias
Secondary to anemia and iron overload
SplenomegalySecondary to extramedullary hemotopoiesis
Can also be due to extravascular hemolysis causing a hypertropic
response in the spleen.
Gallstones Bilirubin stones
•Lifelong hemolytic state causes increased bilirubin deposition in the
gallbladder
Malnutrition Rapidly growing erythrocyte precursors compete for nutrients and can
cause malnutrition
Bronze skin

17. How Are Thalassemias Treated
Treatments for thalassemias depend on the type and severity
of the disorder.
Patients with thalassemia minor usually do not require any
specific treatment. People with β-thalassemia trait should be
warned that their condition can be misdiagnosed as the more
common iron deficiency anemia. They should avoid routine
use of iron supplements; iron deficiency can develop, though,
during pregnancy or from chronic bleeding
Doctors use three standard treatments for moderate and
severe forms of thalassemia. These treatments include blood
transfusions, iron chelation (ke-LAY-shun) therapy, and folic
acid supplements. Other treatments have been developed or
are being tested.

18. Standard Treatments :-
A) Blood Transfusion :
Transfusions of red blood cells are the main treatment for people who have
moderate or severe thalassemias. This treatment gives you healthy red blood cells
with normal hemoglobin.During a blood transfusion, a needle is used to insert an
intravenous (IV) line into one of your blood vessels. Through this line, you receive
healthy blood. The procedure usually takes 1 to 4 hours.Red blood cells live only
for about 120 days. So, you may need repeated transfusions to maintain a healthy
supply of red blood cells.If you have hemoglobin H disease or beta thalassemia
intermedia, you may need blood transfusions on occasion. For example, you may
have transfusions when you have an infection or other illness, or when your
anemia is severe enough to cause tiredness.If you have beta thalassemia major
(Cooley's anemia), you’ll likely need regular blood transfusions (often every 2 to 4
weeks). These transfusions will help you maintain normal hemoglobin and red
blood cell levels, but it's expensive and carries a risk of transmitting infections and
viruses (for example, hepatitis). However, the risk is very low in the United States
because of careful blood screening.

19. B) Iron Chelation Therapy :
The hemoglobin in red blood cells is an iron-rich protein. Thus, regular blood
transfusions can lead to iron overload in the blood and this will damage the liver,
heart, and other parts of the body.
To prevent this damage, doctors use iron chelation therapy to remove excess iron
from the body. Two medicines are used for iron chelation therapy.
1-Deferoxamine is a liquid medicine that's given slowly under the skin, usually
with a small portable pump used overnight. This therapy takes time and can be
mildly painful.

Side effects include problems with vision and hearing.
2-Deferasirox is a pill taken once daily.
Side effects include headache, nausea (feeling sick to the stomach), vomiting,
diarrhea, joint pain, and tiredness

20. C)Folic Acid Supplements :
Folic acid is a B vitamin that helps the body make new red blood cells . Your doctor
may recommend folic acid supplements in addition to treatment with blood
transfusions and/or iron chelation therapy
Other Treatments
Other treatments for thalassemias have been developed or are being tested, but
they're used much less often :
In Beta thalassemia
-Physicians often use splenectomy to decrease transfusion requirements and
the resultant iron overload.
Because postsplenectomy sepsis is possible, defer this procedure until the patient is
older than 6-7 years. In addition, to minimize the risk of postsplenectomy sepsis
,Administer penicillin prophylaxis to children after splenectomy.

21. Cholecystectomy
Patients with thalassemia minor may have bilirubin stones in their gallbladder
and, if symptomatic, may require treatment. Perform a cholecystectomy using a
laparoscope or carry out the procedure at the same time as the splenectomy.


Blood and Marrow Stem Cell Transplant :
the only cure for thalassemia is a procedure called a bone marrow transplant.
Bone marrow, which is found inside bones, produces blood cells. In a bone
marrow transplant, a person is first given high doses of radiation or drugs to
destroy the defective bone marrow. The bone marrow is then replaced with cells
from a compatible donor, usually a healthy sibling or other relative. Bone marrow
transplants carry many risks, so they usually are done only in the most severe
cases of thalassemia.