A novel epsilon gamma delta beta thalassemia presenting with pregnancy complications and severe neonatal anemia

Abstract

We suggest that εγδβ-thalassemia be added to the list of hemoglobinopathies that can cause neonatal anemia and that MLPA of the β-globin cluster be used to confirm its diagnosis. Careful surveillance during pregnancy is important to reduce neonatal mortality and morbidity, especially given the dramatic improvement that occurs later.

First report of εγδβ0‐thalassemia in a Brazilian family

“…1,2 To date, around forty deletions causing εγδβ-thalassemias have been described, mainly in European populations (Figure 1), although few have been fully characterized molecularly because of technical difficulties and the nature of the breakpoints. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Multiplex Ligation- The child's parents, who are clinically asymptomatic, had hematological abnormalities: The mother is heterozygous for HbC [HBB:c.19G>A; p.Glu6Lys (p.Glu7Lys)] and the father has mild anemia with marked microcytosis and hypochromia but without increased Hb A 2 or Hb F levels. The hematological data for the family are shown in Table 1.…”

Identification and molecular characterization of a novel 163 kb deletion: The Italian (ϵγδβ)0-thalassemia

“…To test the significance of these values, we looked for the phenotype of the (εγδβ) 0 -thalassemia carriers from literature (Table 2). [3][4][5][6][16][17][18][19][28][29][30] We compared (i) the Hb A2 values of the 19 (εγδβ) 0 -thalassemia Figure 3 Comparison of the HbA2 and Hb values between (εγδβ) 0 -thalassemia and α 0 -and β 0 -thalassemia carriers. (A) Histogram of the Hb A2 value of 92 heterozygotes for α 0 -thalassemia and of the 19 heterozygotes for (εγδβ) 0 -thalassemia from literature.…”

“…2,3 Up to now, 32 (εγδβ) 0 -thalassemia deletions have been described, but the complete characterization has been achieved in only 14 of them. [3][4][5][6] Adult heterozygotes show a phenotype similar to that of hematological carriers of beta-thalassemia, but with normal levels of Hb A2 due to the loss of one delta locus and normal or minimally increased Hb F; the red cells are relatively more hypochromic and small. The normal levels of Hb A2 make the hematologic phenotype similar to that of carriers of alpha-thalassemia.…”

“…As already described, these deletions are characterized by a moderately severe neonatal hemolytic anemia and they are distinguished from beta-thalassemic patients because they may need red blood cell (RBC) transfusion for the first 6 months of life, but this remits spontaneously with the increasing production of beta-globin in the first year of life. 4 Despite the extreme heterogeneity of the molecular basis of the beta-thalassemia in Italy, the (εγδβ) 0 -thalassemia deletions have never been identified. 7,8 We carried out an epidemiological project on the molecular basis of alpha-thalassemia in Southern Italy and we identified a patient with hematologic phenotype of alpha-thalassemia (microcytosis, polycythemia, and normal Hb A2), which showed normal molecular sequence analysis of the alpha-and beta-globin genes and absence of the most frequent alpha-or beta-thalassemia deletions.…”

State of the art and new developments in molecular diagnostics for hemoglobinopathies in multiethnic societies

“…For the thalassemias, arrays were used to fine‐map the positions of the breakpoint junctions to design gap‐PCR primers for sequencing to determine the exact deletion breakpoints in patients. Furthermore, knowledge of breakpoint sequences might give more insight in the molecular mechanisms giving rise to these rearrangements and may facilitate primer design for gap‐PCR to screen for certain common population‐specific deletions . When designing custom fine‐tiling arrays, it is important to include only unique sequence primers as probes to exclude repetitive sequences which are abundant in the genome.…”