Modification of Hemoglobin H Disease by Sickle Trait

Abstract

A B S T R A C T The rarity of hemoglobin (Hb) H disease in combination with sickle trait may be due in part to the absence ofactual Hb H in individuals who, nonetheless, have inherited the deletion of three a-globin genes. We describe here a boy with persistent microcytic, hypochromic anemia despite adequate iron stores, who exhibited splenomegaly with a normal reticulocyte count and only rare inclusions in circulating erythrocytes. Starch gel electrophoresis and isoelectric focusing at age 5 yr showed 21% Hb S, persistent Hb Bart's, but no Hb H. Recticulocyte a/non-a globin chain synthesis ratio was 0.58 at age 5. The mother (Asian) had laboratory evidence of a-thalassemia trait and the father (Black) had sickle trait. The nature of a-thalassemia in this patient was investigated both by liquid hybridization and by the Southern method of gene mapping, in which DNA is digested with restriction endonucleases and the DNA fragments that contained the a-globin structural gene identified by hybridization with complementary DNA. The patient had only one a-globin structural gene, located in a DNA fragment shorter than that found in normal or a-thalassemia trait individuals, but similar to that present in other patients with Hb H disease. Morphologic studies of bone marrow by light and electron microscopy revealed erythroid hyperplasia with inclusions in polychromatic and orthochromatic erythroblasts, suggesting early precipitation of an unstable hemoglobin. The lack of demonstrable Hb H may be the result of both diminished amounts of(A available for Hb H formation (since one 8-globin gene is (3s) and the greater affinity of a-chains for (3A than 8s-globin chains leading to the formation of relatively more Hb A than Hb S. The pres-

Quantitation of hemoglobin components by high‐performance cation‐exchange liquid chromatography: Its use in diagnosis and in the assessment of cellular distribution of hemoglobin variants

“…with the AS; --/-a genetic condition closely resembles the sixyear-old black-Chinese boy described by Matthay el a1 [17] Pi tetramers in the youngest red cells and not in the older cells isolated from the bottom layers is consistent with the known physico-chemical properties of these abnormal Hbs and may to some extent explain the difficulties in identifying these Hb variants in whole red cell lysates.…”

Alpha-2-Globin Gene Polyadenylation (AATAAA→AATAAG) Mutation in Hemoglobin H Disease among Kuwaitis

“…Matthay et al [23] have suggested that sickle cell trait may modify Hb H disease because the relatively low Hb A level reduces the availability of ␤ -chains to form Hb H.…”

Unusual phenotype of Hemoglobin EE with Hemoglobin H disease: a pitfall in clinical diagnosis and genetic counseling

“…Previously, an unusual EE/Hb H interaction has been observed in a 34-year-old Thai woman 10 who had only 4% of Hb F without Hb Bart, and it has been suggested that the absence of Hb Bart might have been a result of diminished adult level of c-globin expression similar to the temporal decline of Hb F and Bart in an individual with Hb S and a single a-gene. 11 However, previous studies from Thailand demonstrated that Hb Bart in this syndrome could be detected even in the sixth decade of life, 3 and our observation of this ''cinactive'' EE/Hb H in two different age groups suggests that the chronological decreased c-expression seems unlikely. However, this may suggest that there is a different genetic background acting either in cis or in trans on the c-globin expression in these individuals that differentiates them from the majority of cases with EE/Hb H. Study of these unusual cases in greater detail may provide some insights in different genetic heterogeneity of the c-globin expression and persistent production of Hb F in our population.…”