| Alpha Thalassemia States Heterozygous states of alpha thalassemia express themselves as silent carrier (one loci deleted) thalassemia minor (two loci deleted) hemoglobin H disease (three loci deleted) The homozygous state (all four loci deleted), alpha thalassemia major, is incompatible with life. | View Page |
| Defining Thalassemia Thalassemias are named according to the affected gene or globin chain which is showing reduced or absent synthesis. Globin chain loci are found on chromosome 11 (Beta, Delta, Epsilon, and Gamma) chromosome 16 (Alpha, and Zeta) | View Page |
| Defining Alpha Thalassemia Alpha thalassemia demonstrates problems with alpha globin chain production. One to four loci that code for the alpha chain may be deleted from chromosome 16. The greater the number of loci deleted or inactivated, the greater the severity of the anemia which develops. Many different mutations exist that result from partial deletions of alpha genes. This unit of study deals only with the forms of alpha thalassemia that have entire loci deleted. | View Page |
| Thalassemia results from | View Page |
| Alpha Thalassemia Major Gene deletions that cause alpha thalassemia can be homozygous or heterozygous deletions. Homozygous alpha thalassemia (alpha thalassemia major), also known as hydrops fetalis, is a lethal hemoglobin disorder which usually results in stillborn infants. Both alpha chain loci on each chromosome of the pair are deleted, resulting in a total absence of alpha chains. These chains are needed for all normal hemoglobins. If born live, infants with alpha thalassemia major exhibit hepatosplenomegaly, ascites, edema, low birth weight and die within a few hours. Ethnic groups most commonly associated with this form of alpha thalassemia include primarily Southeast Asians and sometimes people of the islands in the Mediterranean. | View Page |
| Alpha Thalassemia Intermedia Alpha thalassemia intermedia (Hemoglobin H Disease) results from a deletion of three out of four alpha chain loci. Infants born with alpha thalassemia intermedia appear normal at birth but often develop anemia and splenomegaly by the end of their first year. Hepatomegaly is not a common finding and there may be some association with mental retardation. Due to the hemolytic nature of this anemia, there may be an increase in respiratory infections, leg ulcers and gallstones. Skeletal changes are not commonly seen in hemoglobin H disease. Every ethnic group can have occurrences of hemoglobin H disease; but it is most often seen in Southeast Asian, the Middle East and the Mediterranean islands. Development and life expectancy are usually normal, but some affected individuals may require splenectomy and transfusion therapy. | View Page |
| Alpha Thalassemia Minor Deletion of two out of four alpha chain loci results in alpha thalassemia minor. The deletions may be homozygous (two on the same chromosome) or heterozygous (one from each of two chromosomes). Alpha thalassemia minor does not produce a clinical disease but may be discovered upon routine testing. Both the homozygous and heterozygous form are common in Southeast Asians. The homozygous form is also seen in American Blacks. | View Page |
| Silent Carrier The Silent Carrier form of alpha thalassemia results from one alpha chain loci deletion. Individuals who are silent carriers show no clinical disease and demonstrate normal results during routine laboratory testing. This form of alpha thalassemia is usually discovered upon family studies. | View Page |
| Normal Chromosome 16 Chromosome 16 contains the genetic codes for the zeta and alpha hemoglobin chains.Each chromosome has two loci alpha chains 1 and 2. This equals a total of four loci of material coding for the alpha hemoglobin chain. See the image for a visual representation of these loci.In the genotypic notation of alpha thalassemia an "" represents the presence of an alpha locus. A "-" represents a deletion of a locus.The notation for the normal number of alpha loci is /. The amount of Hb A produced by this normal gene is 97-98 %.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 16 Alpha Thalassemia Silent Carrier In the Silent Carrier (-/), only one loci is deleted or inactive. Hemoglobin A is still able to be made to its fullest amount, 97-98%.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 16 Alpha thalassemia Minor In alpha thalassemia minor, two loci are deleted or inactive. Either homozygous or heterozygous states are possible. | View Page |
| Chromosome 16 Alpha Thalassemia Intermedia When three loci of alpha chains are deleted (--/-) or inactive, only 70-90% of Hemoglobin A is made. The excess beta chains that remain unpaired form the tetramers of Hemoglobin H.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 16 Alpha Thalassemia Major The complete deletion of alpha chain loci (--/--) in alpha thalassemia major is incompatible with life. None of the vital alpha chains needed for every normal adult hemoglobin can be produced. (drawing modified from Harmening, 1999) | View Page |
| Alpha Thalassemia Minor - Heterozygous In the heterozygous state (--/), one parent contributes a normal gene while the other one a gene with both alpha chain loci deleted.(drawing modified from Harmening, 1999) | View Page |
| Defining Thalassemias Thalassemias are part of a group of 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) | View Page |
| Defining Beta Thalassemia 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. 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. Deletions of additional globin genes coded for on chromosome 11 can result in such combinations as delta-beta thalassemia. | View Page |
| Thalassemia results from which of the following? | View Page |
| 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, a "+" represents a reduction in beta chain production whereas a "0" represents a complete deletion of a locus. The "+s" represents a silent carrier. Delta chain deletions may be present in combination with beta chain deletions.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 11 Beta Thalassemia Intermedia B+s/B+s In Beta thalassemia intermedia, B+s/B+s, 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.(drawing modified from Harmening, 1999) | View Page |
| 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+sIn this state the majority of hemoglobin will be Hb F, with very little Hb A and A2 present.(drawing modified from Harmening, 1999) | View Page |
| 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.(drawing modified from Harmening, 1999) | View Page |