Globin, fetal

Susan Perrtne of the Children s Hospital Oakland Research Center decided to try to reawaken the dormant fetal globin gene. She and her colleagues injected a sodium butyrate solution (the sodium salt of butyric acid) into three sickle cell patients and three (3-thalassemia patients. As a result of the two- to three-week treatment, fetal hemoglobin production was boosted as much as 45% in these individuals. One (3-thalassemia patient even experienced a complete reversal of the symptoms. Moreover, this treatment had few adverse side effects. 

Perrine SP. Fetal globin induction-can it cure beta thalassemia Hematol Am Soc Hematol Educ Program 2005 38-44. 

A man with sickle cell disease and his phenotypically normal wife request genetic testing because they are concerned about the risk for their unborn child. DNA samples from the man and the woman and from fetal cells obtained by amniocentesis are analyzed using the PCR to amplify exon 1 of the p-globin gene. 

Fetal hemoglobin (HbF), which has slightly different Oj binding properties from HbA, is composed of two a- and two y-globin subunits. 

Fetal hemoglobin (HbF) HbF is a tetramer consisting of two a chains identical to those found in HbA, plus two gamma (y) chains (0272, see Figure 3.13). The y chains are members of the p-globin gene family (see p. 35). 

Figure 27-10 Organization of the globin genes on human chromosomes 11 and 16. The composition of the various embryonic, fetal, and adult hemoglobins is also indicated. Closed boxes indicate active genes and open boxes pseudogenes. The triangles ( ) indicate Alu repetitive sequences and their orientation. The shaded boxes indicate Kpn repeat sequences and the half-arrows their respective orientation. The Kpn sequence between the e and 7° genes in fact consists of two tandemly linked Kpn repeats. From Karlsson and Nienhuis196 and Proudfoot.197...

A dominant theme in the treatment of sickle cell disease is the manipulation of the hemoglobin switch from fetal to adult hemoglobin. If the switch did not occur at all or if the y-globin gene did not completely switch to P-globin... 

The continued absorption of iron causes its deposition in various tissues starting with liver and spleen and followed by myocardium. Deposition of iron in the myocardium usually results in death by intractable cardiac failure. Patients suffer from hypoparathyroidism and hypogonadism. Patients with the severe form of thalassemia are more susceptible to bacterial infection, possibly due to the increase in serum iron, which may favor bacterial growth. Iron overload is less common in the adult forms of Q -thalassemia. This is most likely the result of a fundamental difference between a and -thalassemia. As mentioned, the excess of Q -globin chains cannot form viable tetramers and causes red-cell destruction. The excess jS-chains present in a-thalassemia are able to form solnble homodimers and do not precipitate in the bone marrow. This is paralleled in the fetal state when excess y-chains form solnble homodimers. Hence, a-thalassemia is characterized by a severe degree of inefficient erythropoiesis and a milder degree of anemia. 

Figure 31-2 Changes in relative proportions of globin chains at various stages of embryonic, fetal, and postnatal life. (Reprinted from Huehns ER, Dance N, Beaven GH, Hecht F, Motulsky AG.

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