THALASSEMIAS


I. Alpha Thalassemias

  1. Alpha-globin genes are on short arm of chromosome 16. There 2 non-allelic genes on each chromosome, alpha-1 and alpha-2. One or both on each chromosome can be deleted.
  2. Gross gene deletions rather than point mutations are the usual cause of the alpha thalassemias
  3. Silent carrier state: [---- alpha / alpha alpha]. No clinical sequelae. Hb Bart's 0-2% at birth, then none later in life.
  4. Alpha-thalassemia minor. Two of the alpha genes are deleted. Hb Bart's 2-10% at birth, then none later in life. Degree of Hb Bart's depends in part on exact locus of deletion on alpha gene. Mild hypochromic, microcytic anemia. There are two possible forms:
  1. Alpha-thalassemia 1 [---- ---- / alpha alpha] Usually in Asians
  2. Alpha-thalassemia 2 [---- alpha / ---- alpha] Usually in Africans
  1. Hb H disease [---- ---- / ---- alpha]. Usually in Asians. Mild-moderate hypochromic, microcytic anemia. Hemolysis and splenomegaly occur because of accumulation of unpaired beta chains, leading to beta-4 tetramers. Hb Bart?s 10-40% at birth, then trace levels later in life. Severe cases are treated with splenectomy.
  2. Hydrops fetalis [---- ---- / ---- ----] Incompatible with life.

II. Beta Thalassemias

  1. Beta gene cluster is found on short arm of chromosome 11, along with the beta-like genes for the gamma, delta, and epsilon chains
  2. Hb A = alpha2-beta2; Hb A2 = alpha2-delta2; HbF = alpha2-gamma2
  3. Beta thalassemias are usually due to point mutations
  4. Only one beta gene per chromosome 11, unlike the alpha genes
  5. Most common abnormal beta genes:
  1. Beta-zero: no functioning beta subunits, and thus, no HbA, are produced
  2. Beta-plus: some functioning beta subunits are made; Hb is 5-50% HbA
  3. Beta-Lepore: no functioning beta subunits, so no HbA
  1. Beta Thalassemia Minor: state of heterozygosity for any beta-thal gene, i.e. one good beta gene is present. Us. only minor or no anemia, but microcytosis.
  2. Beta Thalassemia Major: state of homozygosity for any beta-thal gene, i.e. both copies of the beta-thal gene are corrupted. Causes severe, transfusion-dependent microcytic anemia (Hb 2-7g/dl; MCV 50-60) with wildly varying RBC size & shape. Presents us. after 1yo b/c HbF is made until then. Presentation includes anemia & failure to thrive, as well as splenomegaly & expansion of marrow spaces, e.g. in bones of face. Frequent transfusion causes iron overload in most. Splenectomy can be helpful. BM transplantation has been used. The Hb produced may include HbA (see above); the rest is HbA2 and HbF