Thalassemia PDF

Thalassemia Made & Presented by: Afnan Shana’ah y Zeina, Lara, Juwana, Sayyaf, Toleen, Jana Supervised by: Dr. Dua’a Quedan  What is thalassemia - Thalassemia is an inherited blood disorder caused when the body doesn’t make enough of a protein (hemoglobin), part of red blood cells. -...

Thalassemia Made & Presented by: Afnan Shana’ah y Zeina, Lara, Juwana, Sayyaf, Toleen, Jana Supervised by: Dr. Dua’a Quedan  What is thalassemia - Thalassemia is an inherited blood disorder caused when the body doesn’t make enough of a protein (hemoglobin), part of red blood cells. - It is the most common human single-gene disorders in the world. - They are a heterogeneous group of diseases of hemoglobin synthesis in which mutations reduce the synthesis or stability of either the α-globin or β-globin chain to cause α- thalassemia or β-thalassemia, respectively - Hemoglobin is composed of : 2 Beta chains + 2 alpha chains Alpha globin protein chains consist of four genes, two from each parent. Beta globin protein chains consist of two genes, one from each parent. - Hemoglobin is the oxygen carrier in red blood cells.  Genetic Basis Thalassemia is inherited in an autosomal recessive pattern. The loss of function of a gene may result from alteration of its coding, regulatory, or other critical sequences due to nucleotide substitutions, deletions, insertions, or rearrangements The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene but do not show symptoms of the condition. The thalassemia type depends on whether the genetic defect occurred in the alpha or beta chain (α or β thalassemia). The extent of the defect will determine the severity of the condition. Pathophysiology Alpha-thalassemia: The most common forms of α-Thalassemia result of gene deletion of alpha encoding goblin chains Mutations occur in the HBA1 and HBA2 genes on chromosome 16 which encode the alpha-globin subunits of hemoglobin causes disruption in the formation of both fetal and adult hemoglobin. In the absence of α-globin chains, the chains from the β-globin cluster are free to form a homo-tetrameric hemoglobin. Pathophysiology Alpha-thalassemia: Missing 1 gene: “Silent” carrier. No signs of illness. Missing 2 genes: Alpha thalassemia trait, mild symptoms of anemia and microcytosis Missing 3 genes: Moderate to severe anemia specifically hemolytic anemia. Missing all 4 genes: Babies who have hydrops fetalis usually die before or shortly after birth. Pathophysiology Beta-thalassemia: The β-thalassemias share many features with α-thalassemia. In β-thalassemia, the decrease in β-globin production causes a hypochromic, microcytic anemia and an imbalance in globin synthesis due to the excess of α chains. The excess α chains are insoluble and precipitate in both red cell precursors and mature red cells causing hemolysis because they damage the cell membrane. The β chain is important only in the postnatal period. In Beta-thalassemia the mutations occur in the HBB gene on chromosome 11 which encodes the beta-globin subunit of hemoglobin. The β-thalassemias are usually due to single base pair substitutions rather than to deletions ( genetic mutations) Pathophysiology Beta-thalassemia: 1 altered gene: A carrier. This condition is called (beta thalassemia trait) or (beta thalassemia minor). It causes mild anemia symptoms. Both genes are altered: (Beta thalassemia intermedia) or (beta thalassemia major/ Cooley's anemia). The intermedia form of the disorder causes moderate anemia. The major form causes serious anemia symptoms.  Epidemiology Thalassemia is most common among persons of Mediterranean, African, Middle Eastern, Indian, Chinese, and Southeast Asian descent. Thalassemias appear to have evolved because they confer heterozygote advantage in providing some resistance to malaria. The prevalence of thalassemia in an ethnic group therefore reflects past and present exposure of a population to malaria.  General Symptoms Iron Overload: Common in beta-thalassemia major and Cardiovascular Bone Deformities: Due to intermedia due to regular Problems: Including heart marrow expansion as the blood transfusions and failure and irregular beats, body attempts to produce increased iron absorption from particularly in those with more red blood cells which the gut. Can lead to heart severe forms of the leads to bone expansion failure, liver disease, diabetes, disease. (face) and endocrine dysfunction. Growth and Infections: Increased Developmental Delays: susceptibility due to Seen in severe cases due splenectomy (removal of to chronic anemia and the spleen) or splenic organomegaly. dysfunction. Many symptoms of the more severe forms of alpha- and beta-thalassemia are quite similar. Each type’s symptoms will differ according to the missing gene and severity of the deleted part.  Symptoms: The symptoms depend on the severity of the mutations which range from asymptomatic to severe symptoms or death. Asymptomatic (no symptoms) No or slight symptoms when one alpha gene is missing. If two alpha genes or one beta gene is missing, the patient might be asymptomatic or mild anemia and fatigue. Mild to moderate symptoms Mild anemia symptoms Delayed puberty. Bone abnormalities. An enlarged spleen Sever symptoms Symptoms of severe anemia include those associated with mild to moderate disease. Additional symptoms may include: Poor appetite. Pale or yellowish skin Urine that’s dark or tea-colored. Irregular bone structure in your face. Diagnosis Moderate and severe thalassemia are often diagnosed in childhood because symptoms usually appear within the first two years of your child’s life A complete blood count (CBC) that includes measures of hemoglobin and the quantity (and size) of red blood cells. People with thalassemia have fewer healthy red blood cells and less hemoglobin than normal. They may also have smaller-than- normal red blood cells. A reticulocyte count (a measure of young red blood cells) may indicate that your bone marrow isn’t producing enough red blood cells. Studies of iron will indicate whether the cause of your anemia is an iron deficiency or thalassemia. Hemoglobin electrophoresis is used to diagnose beta thalassemia. Genetic testing is used to diagnose alpha thalassemia Treatment A blood transfusion. Iron chelation: removal of excess iron from your body Folic acid supplements can help your body make healthy blood cells. Bone marrow and stem cell transplant from a compatible related donor is the only treatment to cure thalassemia. Compatibility means the donor has the same types of proteins, called human leukocyte antigens (HLA), on the surface of their cells as the person receiving the transplant.  Dental Manifestations 1. Maxillary Bone Expansion and Deformities: o Chipmunk Facies: Prominent cheekbones and protrusion of the upper jaw, giving a "chipmunk" appearance. This is due to the expansion of the bone marrow in the maxilla as the body attempts to produce more red blood cells. o Malocclusion: Misalignment of teeth due to altered jaw growth and bone deformities. This can include overbite, underbite, and crowding of teeth. o High Arched Palate 2. Pale Oral Mucosa due to Anemia. 3. Delayed Eruption of Teeth 4. Ulcers and Infections: 5. Dry Mouth (Xerostomia): Salivary Gland Dysfunction: Iron deposition in the salivary glands may impair their function, leading to a dry mouth. This increases the risk of dental caries and periodontal disease.  Dental Management: 1. Anemia and Bleeding Risk: Increased Bleeding Tendency: Severe anemia and potential coagulopathies (bleeding disorders) associated with thalassemia can increase the risk of bleeding during and after dental procedures. Careful hemostatic management is essential. Pre-procedural Blood Work: It may be necessary to assess hemoglobin levels, platelet count, and clotting function before invasive procedures. 2. Infection Risk: Use of antibiotics may be recommended before and after dental procedures. 3. Maxillary Bone Expansion / Bone Deformities / Oral Mucosal Health / Dry mouth 4. Nutritional Support: Ensuring adequate intake of vitamins and minerals that support oral and overall health, such as folate, vitamin B12, and vitamin C. 5. Regular Dental Check-ups: Essential to monitor and manage oral health, particularly due to the risk of infections and bone changes. References THOMPSON & THOMPSON GENETICS IN MEDICINE https://www.cdc.gov/ncbddd/thalassemia/index.html#:~:text=Thalassemia%20is%20an%20inherited%20(i.e.,blood%20transfusions%20and%20chelation%20therapy. file:///C:/Users/user/Downloads/pdfcoffee.com_thompson-thompson-genetics-in-medicine-pdf-free.pdf https://medlineplus.gov/genetics/condition/beta-thalassemia/#:~:t https://thalassemia.ucsf.edu/thalassemia-information https://my.clevelandclinic.org/health/diseases/14508-thalassemias https://www.nhlbi.nih.gov/health/thalassemia/causes https://www.healthline.com/health/alpha-versus-beta-thalassemia#:~:text=Which%20is%20more%20common%2C%20alpha-%20or%20beta- thalassemia%3F%20The,while%20about%201.5%25%20carry%20a%20gene%20for%20beta-thalassemia. https://www.researchgate.net/figure/Estimated-annual-affected-births-of-children-with-b-thalassemia-These-figures-are-from_fig1_47810372 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407235/#:~:text=Thalassemia%20patients'%20gums%20and%20the,reduced%20salivary%20protection%20(22).