Hemoglobin Bart

Hemoglobin Bart s hydrops fetails This occurs due to inheritance of two a-thalassemia-1 allels and the offspring does not have any functional a genes. This condition is incompatible with life and results in stillborn or critically ill fetus with hydrops fetalis. Hemoglobin... 

Hemoglobin Bart s, which is composed of four identical subunits with no heme-heme interaction and Bohr effect, shows CD spectra (240—600 nm) different from those of human adult hemoglobin but similar to those of /S-subunits of the latter (184). 

Electrophoresis of normal and variant hemoglobins. Relative migration distances in starch gel electrophoresis in Tris-EDTA-borate buffer, pH 8.6. Hemoglobin I is the same as H or Hemoglobin Bart s is hemoglobin y. ... 

There are two major molecular variants of thalassemia, the a- and jS-type. In each type, the genetically determined block interferes with biosynthesis of either the a- or jS-chain. j8-Thalassemia is the most common and is associated with a reduction in A (aj ) hemoglobin and an increase in A2 hemoglobin. An a4 tetramer does not usually appear in the blood it is too unstable. In contrast, no A2 is formed in a-thalassemia, and tetramers of either the y-hemoglobin Bart (74) or j8-hemoglobin H P4) may appear in the blood. 

A phosphate buffer system (pH 6.5 - 7.0) Is useful for detecting small quantities of the hemoglobins H and Bart s these variants will both move toward the anode while Hb-A remains at the origin. Figure 3 gives some examples of separations that can be obtained. 

The detection of abnormal hemoglobins In cord blood samples Is usually made with electrophoretic procedures. Four types of hemoglobin variants can be present, namely y-chaln variants, 3-chaln variants, and Hb-Bart s or yif Indicating some form of a-chaln deficiency or a-thalassemla. 

Figure 7.5 Electrophoretic patterns of erythrocyte lysates bearing abnormal hemoglobins. C, A2, S, F, Al7 Barts, and H are hemoglobins C, A2, S (sickle), Aa (normal), Barts and H, respectively. Electrophoresis was done at pH 8.6, the medium was stained with a protein-specific dye, and the bound dye was quantitated densitometrically. Absorbance is on the y axis, distance moved, on the x axis, Shaded areas represent abnormal patterns. (From a circular by Gelman Instrument Co., Ann Arbor, MI, by permission of the copyright holder.)...

Hemoglobin H and Hb Barts are usually found in pathologic conditions, where normal hemoglobin biosynthesis is diminished. This occurs, for instance, in certain types of thalassemias (see Chapter 14). 

The hemoglobin consists mainly of Hb-Bart s (74) and some Hb-H ijSi). Some papers (L18, L22) report the presence of a small amount of normal Hb-A, but this conclusion is based on electrophoretic mobilities only. More recent studies (T8) have offered evidence for the pres-... 

The combination of a-thalassemia with chain variants has frequently been observed w hen associated with Hb-E a well-defined clinical syndrome is present which is primarily found in Thailand (Til, T13, W5). The combination of two a-thalassemia genes (a-Thi and o-Thj) and a single Hb E gene results in a thalassemia intermedia with moderate anemia and hepatosplenomegaly. At time of birth these patients produce some 25% Hb-Bart s, Hb-A, Hb-F, and small amounts of Hb-E. At a later age the disease is characterized by the presence of an increased y chain production and a decreased chain production the hemoglobin phenotype shows some 15% Hb-E, 5-15% Hb-Bart s, and the remainder Hb-A. Hb-H i t) is hardly present as is the tetramer of the yS chain. 

T6. Thumasathit, B., Nondasuta, A., Silpisornkosol, S., Lousuebsakul, B., Unchali-pongse, P., and Mangkornkanok, M., Hydrops fetalis associated with Bart s hemoglobin in northern Thailand. J. Pediat. 73, 132-138 (1968). 

As compared to HbA. Hemoglobins A2, F, Bart s and H have multiple amino acid differences from HbA, and their electrophoretic mobilities depend on the net effect of all these differences on their net charge at pH 8.4-8.6. 

Bart s is y-tetramer and does not function as a normal hemoglobin. 

Although CE instruments are not well designed for CIEF, many variants can be separated better by this technique. In addition to the common variants, G Philadelphia, A2, and Bart s can all be separated by CIEF [46-48]. The separation by CIEF compares well with gel isoelectric focusing and with HPLC. The variants have also been analyzed by both CE and CIEF equipped with special absorption imaging detectors. These types of detection devices eliminate the extra steps needed to move the peaks, after the focusing step, to the detector and can simultaneously detect several capillaries with better precision and faster results than CE instruments. HB A2, which is increased in P-thal, is better quantified by CE compared with AG electrophoresis [44]. Hemoglobin analysis by CE has been reviewed recently [49-51]. 

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