An unusual hemoglobin anomaly and its relation to alpha-thalassemia and hemoglobin-H disease.

A Chinese family with hemoglobin H in the propositus has been reinvestigated. Although the original propositus is now deceased, a sister has the same hematological manifestations. Her hemoglobin, like that of the deceased sister, contains hemoglobins A, H, and Bart's. In addition, however, two minor components have been detected. These minor components appear to have abnormal alpha-chains and are also present in the maternal grandmother, the mother, a maternal aunt, and three other siblings but only in about one-tenth the amount. One of the minor components may be the same as Hb-Thai (25). The father has the characteristics of classical alpha-thalassemia. These results are discussed in relation to current concepts of alpha-thalassemia as they relate to "silent" and "classical" alpha-thalassemia and to possible multiple alpha-chain loci.

Hemoglobin Louisville (beta-42 (CD1) phe-leu): an unstable variant causing mild hemolytic anemia.

An unstable hemoglobin variant termed Hb Louisville, was found in four members of a Caucasian family, who were suffering from a mild hemolytic anemia. The variant showed a decreased stability upon warming at 65 degrees C and an increased tendency to dissociate in the presence of sulfhydryl group-blocking agents. The structural abnormality was identified as a replacement of phenylalanyl residue in position 42 (CD1) by a leucyl residue. Substitution of this phenylalanyl residue, which participates in the contact with heme, by a nonpolar leucyl residue has apparently less severe consequences than a replacement of the same residue by a polar seryl residue as in Hb Hammersmith. Oxygen equilibrium studies of total hemolysate from one Hb Louisville heterozygote indicated a decreased oxygen affinity, a marked decrease in heme-heme interaction, and a normal Bohr effect. Studies with isolated Hb Louisville were not made because it was not possible to separate the variant from normal Hb A.

Some physicochemical properties of hemoglobin-manitoba (alpha2 102Ser replaced by Arg (G9) beta2).

Hb-Manitoba was discovered in 1970 [1] in a Canadian family of British origin. Recently we observed the same variant in a second family, and found that the oxy-derivative of Hb-Manitoba is slightly unstable at 65 degrees C, dissociates less readily at alkaline pH than does Hb-A, and forms asymmetric hybrids with other hemoglobins which are readily detectable by electrophoresis.

Hemoglobin Atlanta or alpha 2 beta 2 75 Leu-Pro (E19): an unstable variant found in several members of a Caucasian family.

Hemoglobin Atlanta, alpha 2 beta 2 75 Leu-Pro (E19), has been found in several members of three generations of a Caucasian family living in metropolitan Atlanta. The abnormal hemoglobin is one of the nine unstable variants in which either a leucyl or an alanyl residue is replaced by a prolyl residue. These substitutions have been observed in the B, E, F, and G helixes of the beta chain and in the H helix of the alpha-chain. Hemoglobin Atlanta heterozygotes are mildly affected by the presence of this unstable hemoglobin.

The unstable hemoglobins: a review.

There are now some 80 known genetic abnormalities controlling the production of unstable hemoglobin variants, including one in the gamma chain. The clinical presentation of patients carrying these variants and the circumstances under which the variants have been detected vary considerably so that no one syndrome covers all cases, but perhaps the best general term is Unstable Hemoglobin Disease (UHD). It must be emphasized, however, that many variants which have been discovered by Hb electrophoresis, and subsequently shown to be heat unstable, do not cause hemolysis in vivo. Some examples of UHD are known as Congenital Heinz Body Hemolytic Anemia (CHBHA) because Heinz bodies are present in large numbers after splenectomy. In many clinical cases of UHD, however, Heinz bodies may not be found. This short review attempts to highlight the different clinical pictures associated with unstable hemoglobins and to discuss their diagnosis. The substitutions and deletions that are associated with heat instability of the hemoglobin molecule are listed with references to the literature.

Rapid cation-exchange high-performance liquid chromatographic procedure for the separation and quantitation of hemoglobins S, C, and O Arab in cord blood samples.

A rapid method for separating and quantitating hemoglobin (Hb) variants in cord blood samples using cation high-performance liquid chromatography (HPLC) is described. The procedure is a modification of a previously published method, and uses a weak cation-exchange Brownlee-3CM column and Bis-Tris-KCN-Na acetate developers. A chromatogram can be completed in 10 minutes. The slow-moving variants, Hbs S, C, and O Arab, can be completely separated from each other and are identified by their elution times relative to Hb A. Hb E elutes as a shoulder on the descending side of Hb A, which is characteristic for this variant in this procedure. Differentiation between heterozygous, homozygous, and Hb X-beta+-thalassemia conditions is easily made.

Hb Camden and Hb Hope found during routine testing.

The electrophoretically fast-moving hemoglobin variant Hb Camden [beta131 (H9) gln leads to glu] has been found in a middle-aged female suffering from pulmonary disease, and Hb Hope [beta136 (H14) gly leads to asp] which migrates just ahead and very close to Hb A was present in a young obstetrical patient with a mild hemolytic anemia.

Hemoglobinopathies observed in the population of the Southeastern United States (SE-USA).

A survey of nearly 250,000 citizens of Georgia and South Carolina conducted during the past twenty years has led to the detection of over 40 abnormal hemoglobins and several additional hemoglobinopathies. The presence of some of these hemoglobin abnormalities cause (severe) clinical symptoms but others remain undetected unless a specific search is initiated. The incidence of Hb S varies slightly among the populations of different areas, and appears to be the highest in the coastal counties of Georgia and South Carolina. A survey of over 17,000 persons of mainly high school and college age has shown that a significant number of cases with clinically significant hemoglobinopathies will remain undetected unless such surveys are actively promoted.