4b Thalassemia syndromes Year 4 Internal Medicine Notes

4b Thalassemia syndromes Year 4 · Internal Medicine Collection: 4TH YEAR ALL NOTES / IMED / IMED 4.2 / Mogere -- Slide 1 Thalassemia syndromes Dr Alex Mogere Consultant Physician Slide 3 INTRODUCTION An autosomal recessive blood disorder Results in excessive destruction of RBCs and further leads to anemia Caused by variant or missing genes that affect how the body make hemoglobin People with thalassemia make less Hb and fewer circulating rbcs than normal,resulting in mild or severe anemia Slide 6 Alpha Thalassemia Results of changes in the genes of the alpha globin component in Hb The w/wide distrbn of inherited alpha thalassemia is corresponding to areas of malaria exposure Slide 7 Aetiology Mutation in the cells that produce Hb Involves the genes HbA1 and HbA2 Mostly inherited in a Mendelian fashion Slide 8 pathophysiology Healthy individuals have 4 alpha globin genes,2 on each chromosome 16 Results when there is disturbance in prdn of alpha globin from 1 or more of the 4 alpha globin genes Genes are responsible for regulating the synthesis and structure of different globins which are divided into 2 clusters The alpha globin genes are encoded on x-mosome 16 and the gamma,delta and b globin genes are encoded on x-mosome 11 A normal person carries a linked pair of alpha globin genes,2 each from maternal and paternal x-mosome Slide 9 Subtypes of alpha thalassemia Alpha thalassemia silent carrier Alpha thalassemia minor trait HbH(HbH) disease Hemoglobin H- constant Spring Hb Bart’s hydrops fetalis Slide 10 Cont.pathophysiology Therefore,alpha thal occurs when there is a disturbance in prdn of alpha globin from any or all 4 of the alpha globin genes When functional point mutations,frame shift mutations, nonsense mutations, and chain termination mutations occur within or around the coding sequences of the alpha –globin gene cluster hb is impaired When that occurs, protein synthesis may be inhibited Slide 11 Cont.pathophysiology Normal prdn of alpha chains is absent which results in excess prdn of gamma globin chains in the fetus and new born or beta-globin chain in children and adults The beta globin chains are capable of forming soluble tetramers(beta-4 or HbH) This form of Hb is still unstable and ppts within the cell, forming insoluble inclusions called Heinz bodies The Heinz bodies damage the RBCs Resulting further in damage to erythrocyte precursors and ineffective erythropoiesis in the Bone marrow, hypochomia, and microcytosis of circulating rbcs Slide 13 Clinical presentation Shortage of RBCs-anemia Weakness Pallor Fatigue Splenomegaly Hepatomegaly Heart defects Leg ulcers Gall stones Abn urinary system /genitalia Hb Bart syndrome can cause complications in pregnancy Hypertension Premature delivery Abnormal bleeding jaundice Slide 14 Cont. Clinical presentation Silent carrier Essentially asymptomatic Normal cbc,mcv,mch,pbf +/- slight hypochromia on microscopy Alpha thal trait Asymptomatic Normal cbc Mcv frequently <80fL.mch always < 27pg Higher RBC count HbH disease Symptoms of chronic hemolytic anemia Often symptomatic at birth High indirect bil, high LDH, low haptoglobin Slide 15 Invxs Silent carrier -cbc unremarkable Alpha thal trait-hb ok, retic normal, mcv-65-76 fL, mch around 22pg HbH-hb 7-10g/dl, Retic count 5-10%,MCV-33-65fL,pbf-hypochromia, microcytosis,target cells Alpha thal with SCA- higher Hb conc and improved rbc survival Geneting testing Slide 16 treatment Involves regular blood transfusions(maintain pt’s Hb at 9-10g/dl) If you receive blood transfusions you should not take Fe supplements…can cause excessive fe build up Chelation therapy, needed after receiving significant no. of transfusions Bone marrow tx in some, esp children(allogeneic hematopoietic stem cell transplantation) Slide 17 Cont tx: Splenectomy if transfusion requirements are increasing(recommended when the calculated annual transfusion requirement is greater then 200-220mlRBCs/Kg/Yr with a hct value of 70%) Surgical/orthodontic correction may be necessary to correct skeletal deformities of the skull and maxilla caused by erythroid hyperplasia Deferoxamine injection Oral/injectable folic acid---possible s/es allergic rxn eg rash,pruritus/swelling,dizziness,breathlessness Slide 18 prevention Prenatal testing Slide 20 Beta thalassemia. X-terized by genetic deficiency in the synthesis of beta globin chains Beta globin is a component of HB 2 major types: thal mjr and thal minor Slide 21 Beta Thal types Thal mjr(Cooley’s anemia) Severe form presence of 2 abn genes that cause either a severe decrease or complete lack of beta globin prdn Thal mnr -presence of one normal gene and one with a mutation Causes mild to moderate mild anemia Slide 22 aetiology Deficiency of beta globin in an autosomal recessive pattern, which means both copies of the HBB(hemoglobin beta ) gene in each cell have mutations Lack of beta globin leads to a reduced amount of functional hb. Without enough hb, rbcs don’t develop normally, causing a shortage of mat