Beta Thalassemia
Case History
A 45 year old Asian woman had blood work done as part of a routine employment physical. Her only complaint was occasional fatigue. Upon review of her CBC, additional blood work was ordered to investigate her microcytosis.
Which of the following genotypes are associated with beta thalassemia minor? More than one answer is correct. Please select all correct answers B/B B+/B B0/B B0/B0
B+/B B0/B feedback: B+/B denotes beta thalassemia minor exhibiting partial deletion of one gene locus and B0/B denotes beta thalassemia minor exhibiting total deletion of one gene locus. B/B denotes a normal beta chain genetic component. B0/B0 represents beta thalassemia major, exhibiting total deletion of both gene loci.
Genotypic System:
B0/B0 B0/B+ B+/B+ B0/B B+/B Bsc/B
Beta Thalassemia Minima
Beta thalassemia minima is typically discovered during family genetic studies. It is genotypically denoted as Bsc/B, for silent carrier. There are no symptoms involved with this condition and significant laboratory findings are absent.
Beta Thalassemia Intermedia
Clinically, beta thalassemia intermedia is midway in severity between major and minor. Growth and development in children with this disorder can usually be considered normal, and most patients have a normal life span; however, some patients have facial bone deformity and/or splenomegaly. Hemoglobin levels are usually decreased with a disproportionately high red blood cell count. Transfusions (again with iron-chelating agents) may be used as a supportive therapy if necessary. Beta thalassemia is attributed to a wide variety of genotypes, including B+/B+, B0/B+, or B0/B. All of the genotypes have in common a significant reduction in the production of the beta-globin chain, with a subsequent reduction in the quantity of HbA.
What other hemoglobin gene loci occur on the same chromosome as the beta chain loci? More than one answer is correct. Please select all correct answers Alpha Delta Gamma Zeta
Delta Gamma feedback: Globin chain loci are found on: chromosome 11 (beta, delta, epsilon, and gamma) chromosome 16 (alpha and zeta)
Chromosome 11 Delta-Beta Thalassemia Minor
Occasionally, the beta chain gene deletion extends to include the locus for the delta chain gene. If this deletion occurs on only one chromosome of the pair, it creates delta-beta thalassemia minor. Delta-Beta 0/ BetaHb A and A2 will both be decreased and Hb F will be increased.
Migration of Hemoglobin in Alkaline Electrophoresis
Of the hemoglobins normally present in an adult, Hb A migrates the fastest, followed by Hb F. Hb A2moves only slightly from the point of origin near the cathode. Abnormal hemoglobins show the following migration patterns: Hb C migrates with Hb A2 near the cathode. Hb S lies between Hb A2 and Hb F. Hb H (4 beta chains) and Bart's hemoglobin (4 gamma chains) are unstable and very fast moving, with Hb H being the faster of the two. They are located nearer the anode past Hb A . Relative migrations of hemoglobin variants on alkaline electrophoresis can be seen below.
Serum Iron
Persons with beta thalassemia may have a slightly increased level of serum iron with a slightly decreased iron binding capacity. The percent of iron saturation is normal to slightly increased.An iron stain of bone marrow usually demonstrates increased levels of hemosiderin. Sideroblasts may be present
With the exception of beta thalassemia minima, which hemoglobin is decreased in beta thalassemia? Hb A Hb A2 Hb F All of these
Hb A feedback: Hemoglobin A is decreased in beta thalassemias with the exception of beta thalassemia minima.
Which hemoglobin will be increased in delta-beta thalassemia? Please select the single best answer Hb A Hb A2 Hb F Hb H
Hb F feedback: HbF is increased in delta-beta thalassemia. It is increased to 100% in delta-beta thalassemia major.
Which of the following is NOT decreased in beta thalassemia major: Please select the single best answer Mean corpuscular hemoglobin concentration (MCHC) Mean corpuscular volume (MCV) Red cell distribution width (RDW) Red blood cell (RBC) count
Red cell distribution width (RDW) feedback: RDW is increased (not decreased) in beta thalassemia major due to anisocytosis and poikilocytosis. RBC count, MCHC and MCV are all decreased in this particular condition.
How is beta thalassemia defined? The production of an abnormal form of hemoglobin due to the substitution of an amino acid in the beta chain. A decrease in the rate of production of Hb A due to a substitution of an amino acid in the beta chain. A decrease in the rate of production of beta chains due to a partial or total deletion of loci from chromosome 11 that code for the beta chain.
A decrease in the rate of production of beta chains due to a partial or total deletion of loci from chromosome 11 that code for the beta chain. feedback; Beta thalassemia demonstrates problems with beta globin chain production. One or two loci that code for the beta chain may be deleted from chromosome 11. The greater the number of loci deleted or inactivated, the greater the severity of the anemia which develops.
Codocytes (target cells) are a typical finding in which of the following types of beta thalassemia? Beta thalassemia minima Beta thalassemia minor Beta thalassemia intermedia Beta thalassemia major
Beta thalassemia minor Beta thalassemia intermedia Beta thalassemia major feedback: Normal red blood cell morphology is usually seen in the silent carrier form of beta thalassemia (minima). All other forms exhibit microcytosis, hypochromia, and codocytes (target cells) along with varying degrees of other abnormal RBC morphologies
Beta Thalassemia Minor
Beta thalassemia minor (one gene mutation or deletion). This condition results in a range in beta chain synthesis from 10 - 50%. Beta thalassemia minor exists in several states that are identified with plus or zero as noted earlier in the course. These notations correlate with the degree of gene deletion or inactivation.Because the delta gene is in close proximity to the beta gene, it is included in the beta thalassemia classification.The following pages include illustrations of beta thalassemia states.
Defining Beta Thalassemia
Beta thalassemia patients demonstrate an inherited defect in beta globin chain production. Since there are two gene loci coding for beta chain production on chromosome 11, there are different forms of beta thalassemia depending on whether one or both loci have been fully or partially affected. The greater the number of loci deleted or inactivated, the greater the severity of the anemia that develops. Many different mutations exist that result from partial deletions of beta genes. This unit of study deals only with the forms of beta thalassemia that have entire loci deleted. In addition, it is important to note that deletions of other globin genes coded for on chromosome 11 can result in combinations as delta-beta thalassemia. There are certain regions of the world where severe forms of beta thalassemia occur more frequently. These include northern Italy, Algeria, Greece, Saudi Arabia, and southeast Asia. Individuals of African descent have a higher frequency of milder forms of beta thalassemia than individuals in other regions of the world.
This image is from a patient with beta thalassemia. Though not diagnostic for this condition, what abnormal RBC morphology is present that would lead you to consider thalassemia? Codocytes (target cells) Spherocytes Macrocytes Acanthocytes
Codocytes (target cells) feedback: Codocytes (target cells) are a common finding in cases of thalassemia. These cells are bell-shaped with an increased surface-to-volume ratio. When codocytes are spread out on a blood smear, the cells have a target-like appearance with a bull's eye in the center. Notice also the uniformity of RBC size and shape on this blood smear. Spherocytes contain more hemoglobin than normal in relation to the cell volume, the opposite of what is seen on this blood smear. Acanthocytes are small, densely stained and irregular shaped red blood cells with unevenly spaced thorn-like or club shaped projections over the surface of the cells. The RBCs in this image are microcytic, not macrocytic. Microcytes are associated with thalassemia.
Delta-Beta Thalassemia
Delta-beta thalassemia exists in both heterozygous and homozygous forms. The symptoms are mild to moderate depending on the severity of the disease and can include mild, hypochromic anemia, slight hepatomegaly and/or splenomegaly and occasional bone changes due to the erythroid hyperplasia. Patients rarely require treatment; however blood transfusions may be necessary in certain cases. In this condition, the body compensates for the lack of beta and delta chain production by increasing the production of gamma globin chains, leading to an increased hemoglobin F level. This form of beta thalassemia can be found in many ethnic groups but is most common in persons from Greece, Africa, and Italy.
Chromosome 11 Delta-Beta Thalassemia Intermedia
Delta-beta thalassemia intermedia exists when both gene loci for beta and delta chains are deleted or inactive on one chromosome, while the other chromosome contains a beta chain gene that is partially deleted or inactive. Delta-Beta 0/ Beta+In this state the majority of hemoglobin will be Hb F, with very little Hb A and A2 present.
A hemoglobin F concentration of 100% may be seen in which beta thalassemia? Please select the single best answer Beta thalassemia minor Beta thalassemia major Delta-beta thalassemia minor Delta-beta thalassemia major
Delta-beta thalassemia major feedback: Delta-beta thalassemia major, Delta-beta 0/ Delta-beta0, exists when both gene loci for beta and delta chains are completely deleted or inactive on both chromosomes. In this state, only Hb F can be made.
Chromosome 11 Delta-Beta Thalassemia Major
Delta-beta thalassemia major, Delta-beta 0/ Delta-beta0, exists when both gene loci for beta and delta chains are completely deleted or inactive on both chromosomes. In this state, only Hb F can be made (two alpha chains, two gamma chains).
Beta Thalassemia Minor
Persons with beta thalassemia minor rarely have physical signs or symptoms caused by this disorder and usually do not require any treatment. Hemoglobin levels may be slightly decreased but with little clinical consequence. A person with beta thalassemia minor has a normal life expectancy. In this type of beta thalassemia, the body is able to produce enough hemoglobin A (due to decreased, but adequate, beta globin chain production) so oxygen delivery is close to normal as is the red blood cell lifespan. The genotypes associated with beta thalassemia minor are B0/B or B+/B.
Laboratory Test Results
The RBC count is increased for the amount of hemoglobin present. The concentration of hemoglobin in the RBCs is slightly decreased (hypochromic) and the cells are small (microcytic). The variation in RBC size (RDW) is within normal limits.
Normal Chromosome 11
Beta chain synthesis is controlled by two gene loci, one on each of chromosome 11. Chromosome 11 also carries the gene loci for delta chains, G-gamma and A-gamma chains, and embryonic epsilon chains. Normal chromosome 11 is depicted in the image below. In the genotypic notation of beta thalassemia, recall that a "+" represents a reduction in beta chain production whereas a "0" represents a complete deletion of a locus. The "+s" or "sc" represents a silent carrier. Delta chain deletions may be present in combination with beta chain deletions.
Beta Thalassemia Genetics Overview
Beta thalassemia forms are classified using two systems: genotypic and phenotypic. The genotypic system classifies the beta thalassemias based on their zygosity (heterozygous vs. homozygous) as well as degree of the mutation (partial vs. full). In this classification system, there are six forms of beta thalassemia. In the phenotypic system, there are four forms of beta thalassemia that are based upon the degree of clinical symptoms experienced by the patient. Key: + = partial deletion or inactivation of gene loci, 0 = full deletion or inactivation of gene loci
Which two of the following beta thalassemia forms are associated with the genotype B0/B+? More than one answer is correct. Please select all correct answers Beta thalassemia silent carrier Beta thalassemia minor Beta thalassemia intermedia Beta thalassemia major
Beta thalassemia intermedia Beta thalassemia major feedback: B0/B+ , or double heterozygous, denotes that there is one completely deleted or inactive beta chain gene and one partially deleted or inactive beta chain gene. This results in beta thalassemia major or intermedia. This genotype causes decreased production of beta chains and can cause severe to moderate symptoms depending on the case.
Beta Thalassemia Intermedia
Beta thalassemia intermedia (homozygous or combined heterozygous for mild gene deletions) displays a level of beta chain production midway between beta thalassemias minor and major.Beta thalassemia intermedia exists in similar states as that of beta thalassemia minor.The following pages illustrate each of these possible states.
Phenotypic System:
Beta thalassemia major Beta thalassemia intermedia Beta thalassemia minor Beta thalassemia minima
Cooley's anemia is another name for which form of beta thalassemia? Please select the single best answer Delta-beta thalassemia Beta thalassemia major Beta thalassemia intermedia Beta thalassemia minor
Beta thalassemia major feedback: Cooley's anemia is another name for beta thalassemia major. Clinical symptoms usually develop during an affected child's first year of life. The child appears to be malnourished and may exhibit abdominal girth expansion. Skeletal deformations are evident, which are a result of increased erythropoiesis. A common finding is facial bone changes. Other clinical signs include frequent infections, hepatomegaly, splenomegaly, cardiomegaly, gall stones, leg ulcers, and poor growth and sexual development. Death usually occurs by the time these patients are in their early twenties unless treated with blood transfusions along with iron-chelating agents.
Nucleated RBCs are most likely to be seen in the peripheral blood of which of these beta thalassemias? Please select the single best answer Beta thalassemia minima Beta thalassemia minor Beta thalassemia intermedia Beta thalassemia major
Beta thalassemia major feedback: Nucleated RBCs may be seen in the peripheral blood in cases of beta thalassemia major. Nucleated RBCs are usually not found in peripheral blood in cases of beta thalassemia minor and beta thalassemia intermedia, and would not be a finding in beta thalassemia minima.
Skeletal deformations are most commonly present in which one of the following beta thalassemia forms? Beta thalassemia minor Beta thalassemia intermedia Beta thalassemia major None of the beta thalassemias All of the beta thalassemias equally
Beta thalassemia major feedback: Skeletal deformations result from the increased erythropoiesis that occurs in beta thalassemia major (see pg. 6, Beta Thalassemia Major). Children with beta thalassemia intermedia may demonstrate some facial bone deformity; however this is not common. Beta thalassemia minor rarely causes any physical signs or symptoms and beta thalassemia minima is completely asymptomatic.
Beta Thalassemia Major
Beta thalassemia major is the most severe type of beta thalassemia. Children with this disease usually develop clinical signs during their first year of life. They appear to be malnourished and may exhibit abdominal girth expansion. They show bone marrow expansion which causes skeletal deformities. This is due to bone marrow compensation for the anemia. A common finding is facial bone changes caused by this bone marrow expansion (sometimes referred to as Mongoloid facial features). Other clinical signs include frequent infections, hepatomegaly, splenomegaly, gall stones, leg ulcers, iron toxicity, and poor growth and sexual development. In addition, cardiac failure due to the increased burden of the heart attempting to oxygenate the tissues can lead to serious complications and death if the condition is not treated. In general, death usually occurs by the time these patients are in their early twenties unless treated. Lifelong blood transfusions, along with iron-chelating agents, are the primary treatments. Bone marrow transplantation has also been effective. The different genotypes associated with beta thalassemia major are B0/B0, B0/B+, or B+/B+. Beta thalassemia major is also referred to as Cooley's anemia.
Chromosome 11 Beta Thalassemia Major
Beta thalassemia major, B0/B0 (two gene mutations, deletions or combination) results in very few to no beta chains being produced.Hemoglobin A levels are at or near 0%. (drawing modified from Harmening, 1999) Other genotypes of beta thalassemia major not depicted include B0/B+ (one beta chain deleted, one partially deleted) and B+/B+ (both beta chain genes partially deleted).
Which beta thalassemia shows no anemia and may not be detected using hemoglobin electrophoresis? Beta thalassemia minima Beta thalassemia minor Beta thalassemia intermedia Beta thalassemia major
Beta thalassemia minima feedback: Beta thalassemia minima (silent carrier) shows no anemia and may not be detected using hemoglobin electrophoresis. The silent carrier state of beta thalassemia, Bsc/B, involves one minor beta chain deletion or mutation. This state produces such a small drop in the level of beta chain synthesis that the alpha to beta chain ratio remains at a near normal state.Hemoglobin A levels remain normal (95% or higher).
Serum Bilirubin
Bilirubin is formed as a result of hemoglobin degradation. Normally, senescent red blood cells are removed from circulation and the bilirubin that is formed is processed by the liver. The normal level of serum bilirubin for adults is 0.2-1.0 mg/dL.Bilirubin levels increase with some liver disorders and also in anemia that is a result of a hemolytic process. Patients may display jaundice when serum bilirubin levels exceed 2.0 mg/dL.Persons with beta thalassemia major usually have an increased bilirubin level. This bilirubin is typically the unconjugated fraction of bilirubin.
This is a representative field from the patient's peripheral blood smear. What RBC morphology is prominent on this patient's smear? Spherocytes Codocytes (target cells) Acanthocytes Schistocytes
Codocytes (target cells) feedback: The red cells that are prominent on this blood smear are codocytes, also referred to as target cells. Codocytes are a common finding in cases of thalassemia. These cells are bell-shaped with an increased surface-to-volume ratio. When codocytes are spread out on a blood smear, the cells have a target-like appearance with a bull's eye in the center. Notice also the uniformity of RBC size and shape on this blood smear (see pg. 35, Laboratory Test Results). Spherocytes contain more hemoglobin than normal in relation to the cell volume, the opposite of what is seen on this blood smear. Acanthocytes are small, densely stained and irregularly shaped red blood cells with unevenly spaced thorn-like or club-shaped projections over the surface of the cells. Schistocytes are fragments of red blood cells that may be triangular, helmet, or irregular in shape. They are evidence of mechanical damage to the red blood cells.
Hemoglobin Electrophoresis Theory
Hemoglobin electrophoresis is the movement of hemoglobin proteins in an electric field at a fixed pH.Because the various hemoglobins are comprised of different combinations of globin chains (normal or abnormal), they will demonstrate different degrees of mobility. Typically, when thalassemia or hemoglobinopathy is suspected, alkaline electrophoresis is performed, which may be confirmed with acid electrophoresis.For alkaline hemoglobin electrophoresis, a hemolysate is applied to cellulose acetate, which is electrophoresed in a buffer at pH 8.4-8.6. At this pH, hemoglobin proteins move from cathode to anode. The proteins are visualized by the application of a dye, which also makes them measurable by densitometry.
Hematologic Findings For Various Types of Beta Thalassemia
If red blood cells are normochromic and normocytic, the RBC, Hb, and Hematocrit (HCT) test values follow in three-fold progression (i.e., RBC x 3 = Hb and Hb x 3 = HCT). This is sometimes referred to as "the rule of threes." This rule will usually not apply in cases of beta thalassemia, particularly beta thalassemia minor where the RBCs are not normochromic and are microcytic, and where there is a disproportionate number of RBCs for the amount of hemoglobin that is present. The RDW reflects the variation in size of the RBCs. This helps to differentiate among various microcytic anemias. Most heterozygous forms of inherited anemias (thalassemias and hemoglobinopathies) demonstrate a uniformity of size and shape, thus keeping RBC size variation to a minimum and the RDW within normal limits.
The CBC results in this case break the rule of three. What is the rule of three? All abnormal cell counts should be repeated two more times to verify the results. The RBC count is generally three times greater than the hemoglobin .If red blood cells are normochromic and normocytic, the hemoglobin times 3 will approximately equal the HCT. The indices, MCV, MCH, and MCHC all reflect the same direction of results (normal, increased, or decreased)
If red blood cells are normochromic and normocytic, the hemoglobin times 3 will approximately equal the HCT. feedback: he rule of three is a mathematical check to ensure the accuracy of hemoglobin and hematocrit test results. When performing a CBC, if the red blood cells (RBCs) are normochromic and normocytic, the hemoglobin x 3 should approximate the hematocrit result (see pg. 35, Laboratory Test Results). The increased number of RBCs and the decreased hemoglobin in this case study prevent the "rule of three" from being successfully applied.
Chromosome 11 Beta Thalassemia Intermedia B+/B+
In Beta thalassemia intermedia, B+/B+, both beta chain loci show a partial deletion or inactivation of the gene.Hemoglobin A is made to only 55% to 75% of its normal amount.
Chromosome 11 Beta Thalassemia Minor B+/B
In Beta thalassemia minor B+/B one beta gene locus is partially deleted or inactive. With this deletion, only 85% to 95% of the normal level of Hb A is made
Chromosome 11 Beta Thalassemia Minor B0/B
In Beta thalassemia minor, B0/B, one beta gene locus is completely deleted or inactive.Hemoglobin A production is down to 70% - 85% in this state of beta thalassemia.
Chromosome 11 Beta Thalassemia Intermedia B0/B+, B0/B
In beta thalassemia intermedia B0/B+, there is one completely deleted or inactive beta chain gene, while the other is partially deleted or inactive.This state also results in Hb A production of 55%-75% of normal. (drawing modified from Harmening, 1999) In beta thalassemia intermedia B0/B, there is one completely deleted or inactive beta chain gene, while the other gene is completely normal. (not shown)
What clinical characteristics might a person with beta thalassemia intermedia exhibit? Please select the single best answer Severe facial distortions Shortened life-span Some splenomegaly None of these
Some splenomegaly feedback: Growth and development in children with beta thalassemia intermedia is usually normal and most patients have a normal life span. However, they can demonstrate splenomegaly and some facial bone deformity.
Defining Thalassemias
Thalassemias are part of a group of quantitative hemoglobin synthesis disorders in which a defect exists in the rate of production of one or more of the globin chains. This defect results from either a heterozygous or homozygous deletion or inactivation of a globin chain gene. Thalassemias are named according to the affected gene or the globin chain that is showing reduced or absent synthesis.Globin chain loci are found on: chromosome 11 (beta, delta, epsilon, and gamma) chromosome 16 (alpha, and zeta)
Why is it important to note that the red cell distribution width (RDW) in this case is normal ? The RDW adds nothing to the interpretation of these results. The RDW helps to differentiate among various types of microcytic anemias. A normal RDW rules out the possibility of a heterozygous inherited anemia such as thalassemia minor. The RDW is usually normal for microcytic, hypochromic anemias.
The RDW helps to differentiate among various types of microcytic anemias. feedback: The RDW helps to differentiate among various microcytic anemias. The RDW reflects the variation in size of the RBCs. Most heterozygous forms of inherited anemias (thalassemias and hemoglobinopathies) demonstrate a uniformity of size and shape, thus keeping RBC size variation to a minimum and the RDW within normal limits (see pg. 35, Laboratory Test Results). In acquired anemias, there is usually a high variation in RBC size. This may be the result of nutrient deficiency that unequally affects red blood cells, or it may be the result of various red cell destruction mechanisms. Homozygous forms of inherited anemias may also exhibit a variation in RBC size. In all of these cases, the RDW would be abnormal.
Hemoglobin Electrophoresis Patterns in Beta Thalassemia
The following list corresponds to this image of alkaline hemoglobin electrophoresis.Lanes 1 and 2: normal patient specimenHb A is over 98%, with a small amount of Hb A2 visible.Lanes 3 and 4: Beta thalassemia minorHb A is decreased to 94%, Hb A2 is increased at 5%, and Hb F is 1%Lanes 5 and 6: Delta-beta thalassemia majorNo Hb A or A2 is present, Hb F is 100%Lanes 7 & 8: Delta-beta thalassemia intermediaHb A is 8.5%, Hb A2 is 3.5% and Hb F is 88%Lane 9: AF control Lane 10: ASC control(Remember, AF and ASC are labels and do not indicate the order of migration.)
Case History Summary
The laboratory findings in this case represent classic findings seen in beta thalassemia minor including: erythrocytosis, decreased hemoglobin, normal hematocrit, normal RDW, and the presence of codocytes (target cells). This patient does have a mild anemia, but some patients with beta thalassemia minor have no anemia. Hemoglobin electrophoresis confirms this diagnosis, showing an increased Hb A2 level and decreased Hb A.In addition, the slightly increased iron and slightly decreased TIBC contradict a suspicion of iron deficiency. These chemistry results are typical for beta thalassemia, even though the red blood cells are microcytic and hypochromic.
Chromosome 11 Beta Thalassemia Minima (Silent Carrier) Bsc/B
The silent carrier state of beta thalassemia (beta thalassemia minima), Bsc/B, involves one minor beta chain deletion or mutation. This state produces such a small drop in the level of beta chain synthesis that the alpha to beta chain ratio remains at a near normal state.Hemoglobin A levels remain normal (98% or higher).
Anemia in Beta Thalassemia
There is often an excess production or accumulation of globin chains in thalassemias whose genes are not affected by the deletion. In beta thalassemia, this may be seen as an increase in gamma chain and delta chain production, leading to increased levels of hemoglobin F and A2, respectively. These hemoglobins have a higher oxygen affinity, leading to decreased oxygenation of the tissues and clinical symptoms respective to this state. In addition, the excess free alpha chains produced in this condition form insoluble precipitates within the red blood cells, often causing red cell membrane damage and decreased cellular deformability. This leads to hemolytic anemia. Adding to the anemia is a decrease in the total amount of hemoglobin produced in spite of the erythroid hyperplasia of the bone marrow.
Normal Hemoglobin Electrophoresis
This electrophoresis gel displays the migration patterns for a person with normal hemoglobin distribution. Normally Hb A is present in excess of 95% with the remaining being made up of Hb A2 and Hb F.Here you can see the large band of Hb A with a faint band in the Hb F and Hb A2 regions.Controls for A and F and A, S, and C are included.(AF and ASC are simply labels for the controls and do not indicate order of migration.)
Which chromosome demonstrates a partial or full gene loci deletion in various forms of beta thalassemia? Chromosome 6 Chromosome 8 Chromosome 11 Chromosome 9
chromosome 11 feedback: Beta thalassemia is the result of one or more gene loci deletions or inactivations on chromosome 11. These loci code for the production of beta globin chains, which are a main component of hemoglobin A. In beta thalassemia, when gene loci on chromosome 11 are deleted or inactivated, the body cannot produce adequate amounts of beta globin chains and compensates by producing increased gamma and delta globin chains instead