beta thalassemia is a genetic disorder where there's a deficiency in production of the beta-globin chains of hemoglobin which are the oxygen-carrying proteins in red blood cells or rbcs for short beta-thalassemia is most commonly seen in mediterranean african and southeast asian populations normally hemoglobin is made up of four globin chains each bound to a heme group there are four major globin chain types alpha beta gamma and delta these four globin chains combine in different ways to give rise to the different kinds of hemoglobin first there's hemoglobin f or hbf where f stands for fetal hemoglobin and that's made up of two alpha globin and two gamma globin chains hemoglobin a or hva the major adult hemoglobin form is made up of two alpha globin and two beta-globin chains finally hemoglobin a2 or hba2 accounts for a small fraction of adult hemoglobin in the blood and it's made up of two alphaglobin and two delta globin chains with beta thalassemia there's either a partial or complete beta globin chain deficiency due to a point mutation which is when a single nucleotide in dna is replaced by another nucleotide in the beta-globin gene present on chromosome 11. and most often these mutations occur in two regions of the gene called the promoter sequences and splice sites which affects the way the mrna is read the result is either reduced or completely absent beta globin chain synthesis and since this is an autosomal recessive disease two mutated copies of this gene one from each parent are needed to develop the disease if the person has just one mutated gene that codes for either a reduced production or absent production of beta-globin chains then they have beta thalassemia minor if the person has two mutated genes that code for reduced beta globin chain synthesis then they're said to have beta thalassemia intermedia if the person has two beta zero mutations then no beta-globin chains are produced and they're said to have beta thalassemia major when there's a beta-globin chain deficiency free alpha chains accumulate within red blood cells and they clump together to form intracellular inclusions which damage the red blood cell cell membrane this causes hemolysis or red blood cell breakdown in the bone marrow or extravascular hemolysis where red blood cells are destroyed by macrophages in the spleen hemolysis causes hemoglobin to spill out directly into the plasma where heme is recycled into iron and unconjugated bilirubin over time the excess unconjugated bilirubin leads to jaundice and excess iron deposits leads to secondary hemochromatosis at the same time hemolysis leads to hypoxia because there are fewer red blood cells to carry oxygen to organs and tissues and a consequence of hypoxia is that it signals the bone marrow and extra medullary tissues like the liver and spleen to increase red blood cell production which may cause bone marrow containing bones like those in the skull and face as well as the liver and spleen to enlarge okay now beta thalassaemia minor is usually asymptomatic on the other hand with beta thalassemia major symptoms do not develop until the first three to six months of life that's because during the first three to six months of life fetal hemoglobin is still produced and that process uses up some of the free alpha chains common beta thalassemia major signs and symptoms include symptoms of anemia like power shortness of breath and easy fatigue ability jaundice swollen abdomen due to an enlarged liver and spleen hepatosplenomegaly and growth retardation complications due to hemochromatosis include arrhythmias pericarditis cirrhosis hypothyroidism and diabetes mellitus other beta thalassemia major findings may include enlarged forehead and cheekbones which is called chipmunk faces on a skull x-ray the skull bones show a radiolucent bone marrow with fine hair-like projections that look a bit how the hair on your arms stand up when you get the goosebumps so it's called hair on end appearance alternatively this is also called a crew cut appearance named after the type of haircut diagnosis of beta thalassemia usually begins with a routine blood test that shows a low hemoglobin level decreased mean corpuscular volume or mcv and a high red blood cell distribution width or rdw which indicates that the red blood cells come in a lot of different sizes however the rdw is often normal with beta thalassemia minor the peripheral blood smear shows microacidic or small and hypochromic or pale red blood cells there are also target cells which are small red blood cells that look like bull's eyes due to scrunching up of the excess cell membrane lab work may also show high serum iron high ferritin and a high transfer and saturation level finally the diagnosis is confirmed with hemoglobin electrophoresis which shows low amounts of hba but an increase in hbf and hba2 levels which are formed when excess alpha chains start binding to gamma and delta chains in beta thalassaemia minor there's usually an increased hba2 level greater than 3.5 percent on gel electrophoresis beta thalassemia does not always require treatment but when needed blood transfusions are given to correct low hemoglobin levels and associated symptoms based on the need for blood transfusion there are two clinically relevant categories of beta thalassemia first there's the transfusion dependent thalassemia category which refers to all the phenotypes that require recurrent blood transfusions for survival this category includes beta thalassemia major and sometimes intermediate beta thalassemia with severely reduced beta chain synthesis the second category is that of non-transfusion-dependent thalassemia which refers to thalassemias that do not require regular blood transfusions this category includes beta thalassemia minor and beta thalassemia intermedia with milder symptoms keep in mind that regular blood transfusions add up to the iron overload which can worsen hemochromatosis to prevent this iron key weighting agents like deforoxamine are given which trap some of the excess iron and sweep it away through feces or urine finally a splenectomy can be done when splenomegaly causes excess hemolysis beta thalassemia is an autosomal recessive disorder caused by a mutation in the beta-globin gene present on chromosome 11 which results in reduced or completely absent beta-globin chain synthesis there are three types beta thalassemia minor intermedia and major beta thalassemia major causes chipmunk faces hair on end appearance on a skull x-ray hepatosplenomegaly jaundice and secondary hemochromatosis