Hb Barts

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. 

Hb-B0Jut 6 OK yif can best be demonstrated by either cellulose acetate or starch gel electrophoresis. The amount of Hb-Bart s can differ from 1% to over 80% dependent on the abnormality Involved. Quantitative determination Is most accurately made by CM-Cellulose or CM-Sephadex chromatography. 

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 newborn with Hb-H disease produces about 25% Hb-Bart s and only small quantities of Hb-H. This 74 is slowly disappearing during the first 6 months of life. Small amounts of a 84 component have also been isolated from blood of adult patients with Hb-H disease (D3). The clinical, biochemical, and hematological manifestations are indeed consistent with the hypothesis that Hb-H disease results from a double heterozygosity for the a-Th, and the a-Thj genes. 

Small quantities (less than 1%) of Hb-Bart s are often observed in blood from Negro newborns (HIO, H22, S3) the incidence approaches the 20%. In some babies a larger amount (up to 5%) is present. The -chain deficiency does not express itself beyond infancy. Because Hb-H disease and hydrops fetalis have not been found in the Negro, it seems that either the a-Th2 type or an additional type of a-thalassemia is present. The babies with the higher amounts of Hb-Bart s are considered to be homozygous for the deficiency and those with the minute amounts heterozygous. 

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. 

R25. Ronisch, P., and Kleihauer, E., Alpha-thalassamie mit Hb-H und Hb Bart s in einer deutschen Familie. Klin. Wochenschr. 23, 1193-1200 (1967). 

Figure 31-12 HPLC chromatograms obtained on the Bio-Rad Variant p-Tha short program for a, Hb Bart s b, pAthaiassemia major c, B -thalassemia homozygous E d, Hb H e, homozygous S f,S trait g, homozygous C h, C trait /, Hb S-Hb G Philadelphia, (from Qarke GM, Trefor N, Higgins TN. Laboratory Investigation of Hemogiobinopatbies and Thalassemias Review and Update. Clin Chem 2000 46 1284-90.)...

Hb Bart s. Hb Bart s results from deletion of aU four a-globin genes with the subsequent inability to produce any a-globin chains that leads to failure of synthesis of Hbs A, F, or A2. In the fetus there is an excess of y-globin chains that join together to form unstable tetramers known as Hb... 

Bart s (y ). Mothers carrying a fetus with Hb Bart s usually present clinically between 20 and 26 weeks gestation with pregnancy-induced hypertension and polyhydramnios. Ultrasound of the fetus shows hydrops. Severe anemia (Hb usually <80g/L) is noted on a fetal blood sample obtained by cordocentesis. It is important to rule out other causes for the hydropic fetus by performing TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex) testing. 

HPLC analysis of a cordocentesis blood sample shows one or two. very sharp and narrow peaks at the injection point on the chromatogram (Figure 31-12, a). The major band is Hb Bart s with a smaller band attributed to Hb Portland. There is a complete absence of Hb E Alkaline electrophoresis shows a band migrating at or close to the solvent front (Hb Bart s) with another band in the Hb A position (Hb Portland). 

Hb Bart s hydrops fetalis is almost invariably fatal,with some fetuses dying in utero and others surviving a few hours after birth. Treatment using intrauterine transfusion has had very limited success, with potential complications in the children of growth retardation and severe brain damage, which may possibly be related to long-standing intrauterine anemia. 

Hb "Barts yyyy Resembles thallasemia strong inhibition of... 

---