Date of Presentation: September 23rd, 2014
Date of Sign-up: September 9th, 2014
Instructor: Dr. Jeffrey Henderson
THALASSEMIA
Chia-En Joanne Chang
Amanda Chow
Ju Pan (Harmony) Hsieh
Linda Xi Yang
WHAT IS THALASSEMIA?
Source: http://thalassemia.com/images/thalassemia-word-cloud.png
Sources: http://bio1151b.nicerweb.com/Locked/media/ch05/05_21gProteinHemoglobin-L.jpg
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CAUSES OF THALASSEMIA
• Alpha-Thalassemia:
• Deletion in one or more of the 2 alpha-globin genes (HBA1 and HBA2) of
chromosome 16
Silent Carriers
1 gene deletion
Hemoglobin H (HbH) disease
3 gene deletions
Alpha-thalassemia trait
2 gene deletions
Hemoglobin Bart hydrops fetalis
syndrome
All 4 genes deleted
• Amount of mutation corresponds to severity of disease
CAUSES OF THALASSEMIA
• Beta-Thalassemia:
• Point mutation in the beta-globin gene of chromosome 11
Thalassemia minor
1 gene mutation
Thalassemia intermedia/major
Both genes mutated
• Amount of mutation corresponds to severity of disease
SYMPTOMS
Fussiness
Fatigue
Loss of Appetite
Jaundice
Paleness
http://images.agoramedia.com/wte3.0/gcms/Fussy-Babies-300x300.jpg, http://atlascorrectionboise.com/wp-content/uploads/2014/01/fatiguedwoman.jpg, http://www.kidscenter.org/images/10415990/Jaundice-In-Newborn-Babies.jpg, http://images2.fanpop.com/image/photos/13300000/Edward-In-Eclipse-edward-cullen-13333892-2217-1599.jpg
COMPLICATIONS
Bone formation/puberty
Frequent infections
Liver failure
Heart failure
Enlarged Spleen
http://bionews-tx.com/wp-content/uploads/2013/07/liver-failure.jpg http://blogs.independent.co.uk/wp-content/uploads/2012/06/090105101501-large.jpg, http://renovathx.com/wpcontent/uploads/2012/10/cropscisource_bh5041-31a1b4a59e737514549cca29e838f74f2dcf947a-s6-c30.jpg, http://drbcshah.com/wp-content/uploads/2013/02/spleen.jpg,
Clinical Manifestation of [beta]-Thalassemia/Hemoglobin E Disease
METHOD OF DIAGNOSIS
• Before diagnosing a patient with thalassemia, the doctor
will consider:
• a) your family background
• b) your ethnic group
• c) whether your anemia is due to iron-deficiency instead of
thalassemia
• To diagnose thalassemias, doctors can use both:
• 1) A (CBC) or complete blood count test to look for fewer
than normal numbers of red blood cells, smaller red blood
cells and low levels of hemoglobin.
• 2) Hemoglobin test to look for mutated alpha or beta
globin chains
http://images.wisegeek.com/vials-of-blood.jpg http://www.familyholiday.net/wp-content/uploads/2012/05/Family-Tree-craft-Template-Ideas_15.jpg
ALPHA-THALASSEMIA TREATMENTS
• Silent carriers & alpha-thalassemia trait
• No treatment required
• Hemoglobin H disease
• Red blood cell transfusion
• Replenishes red blood cells lost due to hemolytic anemia
• Folic acid supplements
• Aids in production of normal red blood cells
• Hemoglobin Bart hydrops fetalis syndrome
• No current treatment known
http://www.optimumchoices.com/images/Blood%20transfusion_.jpg
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BETA-THALASSEMIA TREATMENTS
• Thalassemia minor/intermedia
• No treatment required
• Thalassemia major
• Red blood cell transfusions
• Replenishes red blood cells
• Iron chelating
• Removes excess iron
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BONE MARROW TRANSPLANT
• Only known cure
• Limitations:
• Requires identical match for transplantation
• Patient must have no high risk complication factors
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PROGNOSIS: LIFESTYLE
To keep a healthy and more normal lifestyle, people with
thalassemia must:
•1) Continue with blood transfusions or iron chelation
medication treatments to avoid iron buildup, which can
lead to organ failure and death
•2) Get regular checkups for blood cell counts, iron levels,
heart, liver and viral infection tests
•3) Talk about feelings of stress, anxiety, fear or depression
with your doctor, patient support groups, family and
friends.
•4) Look for a genetic counselor if you plan on having
children
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RECENT RESEARCH
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Thalassemia
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D
F
T
Children's Hospital & Research Center Oakland. "Welcome to Thalassemia.com." Northern California
Comprehensive Thalassemia Center. N.p., n.d. Web. 12 Sept. 2014.
<http://www.thalassemia.com/>.
Cooley's Anemia Foundation. "About Thalassemia." Cooley's Anemia Foundation. N.p., n.d. Web. 13
Sept. 2014. <http://www.thalassemia.org/learn-about-thalassemia/about-thalassemia/>.
Fucharoen, Suthat et al. "Clinical Manifestation of Beta-Thalassemia/Hemoglobin." Journal of Pediatric Hematology/Oncology 22.6 (2000): 552-557. Print.
Galanello, Renzo, and Antonio Cao. "Alpha-thalassemia." Genetics in Medicine 13 (2011): 83-88. Print.
Galanello, Renzo, and Raffaella Origa. "Beta-Thalassemia." Orphanet Journal of Rare Diseases 5.11 (2010): n. pag. OJRD. Web. 12 Sept. 2014.
Gersten, Todd. "Hemolysis: MedlinePlus." Hemolysis . U.S. National Library of Medicine, n.d. Web. 12
Sept. 2014. <http://www.nlm.nih.gov/medlineplus/ency/article/002372.htm>.
Leung, Kathryn . "Allogeneic Stem Cell Transplantation, Severe Homzygous 0/+Thalassemia or Sever Variants of Beta 0/+ Thalassemia, THALLO." ClinicalTrials.gov.
US National Institutes of Health, n.d. Web. 16 Sept. 2014. <http://www.clinicaltrials.gov/ct2/show/NCT00578292?term=Thalassemia&rank=4>.
Lucarelli, G., M. Andreani, and E. Angelucci. "The cure of thalassemia by bone marrow transplantation." Blood Reviews 16 (2002): 81-85. Print.
Mednick, Lauren, et al. "Symptoms of depression and anxiety in patients with thalassemia: Prevalence and correlates in the thalassemia longitudinal cohort."
American Journal of Hematology 85.10 (2010): 802-805. Print.
National Center on Birth Defects and Developmental Disabilities. "Thalassemia ." National Center on
Birth Defects and Developmental Disabilities . N.p., n.d. Web. 12 Sept. 2014.
<http://www.cdc.gov/ncbddd/blooddisorders/documents/bbv_pnv_c0_1159_thalassemia_r
2mtr.pdf>.
National Human Genome Research Institute. "Learning About Thalassemia." National Human
Genome Research Institute. N.p., n.d. Web. 13 Sept. 2014. <http://www.genome.gov/10001221>.
National Institute of Health. "What Are Thalassemias?." National Heart, Lung and Blood Institute. N.p., n.d. Web. 12
Sept. 2014. <http://www.nhlbi.nih.gov/health/health-topics/topics/thalassemia/>.
S., Navaneetha Krishnan, Shaji G. , Ravalya P., and Nazia SK. "Management of Thalassemia." International Research Journal of Pharmacy 4.10 (2013): 1-3. Print.
"Scientists advance a two-gene approach to curing beta-thalassemia." St Jude Children's Research Hospital. N.p., n.d. Web. 15 Sept. 2014.
<http://www.stjude.org/stjude/v/index.jsp?vgnextoid=776e08eef1583210VgnVCM1000001e0215acRCRD&vgnextchannel=de2eecf652abe210V
gnVCM1000001e0215acRCRD>.
Thalassemia Foundation of Canada. "Clinical Trial Updates." Thalassemia Foundation of Canada . N.p., n.d. Web.
12 Sept. 2014. <http://www.thalassemia.ca/medical-updates/test-post-4/>.
CITATIONS
Thalassemia: genetic blood disorder causing an abnormally low functional hemoglobin or number of erythrocytes
SUMMARY
2 major types of Thalassemia with subclasses within each type:
oAlpha thalassemia - a defect in one or more of the alpha subunits. Occur most often in Southeast Asia, the Middle East, China, and African descent.
 Most prominently caused by deletion in either or both genes coding for the alpha globin subunits
 Inherited in an autosomal (Mendelian) recessive manner
 Has 4 forms of varying severity depending on presence of functioning alpha genes:
1) Silent carrier: one alpha globin gene deletion, generally normal phenotype
2) Alpha-thalassemia: one or two alpha globin gene deletions, deletions can be cis or trans
3) Hemoglobin H (HbH) disease: only one functional alpha globin gene present
4) Hemoglobin Bart hydrops fetalis syndrome: absence of all 4 alpha globin genes, fetuses are usually stillborn
oBeta thalassemia - a defect in one or more of the beta subunits. Occur most often in Mediterranean origin, and to a lesser extent, Chinese, other Asians and
African Americans
 Caused by point mutations in the beta-globin gene.
 Genes are inherited in an autosomal (Mendelian) recessive manner
 Has 3 forms of varying severity
1) Thalassemia minor: Heterozygous, one good beta gene and one defective. Usually no symptoms but can cause minor anemia.
2) Thalassemia intermedia: Homozygous, both defective beta gene. Less severe symptoms no blood transfusions required.
3) Thalassemia major: Homozygous, both defective beta gene. More severe symptoms, does require blood transfusion.
Symptoms are severity-dependent and can include: fussiness, paleness, frequent infections, poor appetite, failure to thrive, failure to thrive, jaundice
(yellowing of the skin and whites of the eyes), enlarged organs, malnourishment, and depression. Alpha thalassemia may also have bone growth problems at
the cheeks, forehead and jaws; while patients with the most severe form of alpha thalassemia (hydrops fetalis) are stillborn or die shorty after being born.
Patients looking to have children should talk to a genetic counselor
Diagnosis: Doctors diagnose thalassemias using 1) a CBC(complete blood count test) to look for low RBC numbers, smaller than usual RBC and low hemoglobin
as well as 2) a hemoglobin test to look for mutated alpha or beta globin chains.
Treatment: Continue blood transfusions, iron chelation, regular checkups, and vitamin supplement intake.
Cure: bone marrow transplant.