Letter to the Editor SMJ
Changes in HbA2 Levels May Signify Hemoglobin
Defects in Infants
To the editor:
(13.4%) were heterozygous for HbE, 18 (12.7%) were
Te hemoglobin profile has been utilized as a clue for
heterozygous for α-thalassemia 1, and 9 (6.3%) were
the diagnosis of thalassemia and hemoglobinopathy. Fetal
deletional HbH disease caused by compound heterozygous
hemoglobin (HbF, α2γ2) is highly expressed as the major
α-thalassemia 1 with α-thalassemia 2 (Table 1). Complete
functional hemoglobin during the fetal stage. Following
blood count (CBC) showed hypochromic microcytic
hemoglobin switching, HbF declines to less than 1%
anemia with reduced total Hb level, Hct, MCV, and
of the total hemoglobin within one year of age. Adult
mean corpuscular hemoglobin (MCH) (Table 1). On
hemoglobin (HbA, α2β2) therefore predominates over total
average, the hemoglobin profile of normal infants was
hemoglobin in combination with 2-3% of HbA2 (α2β2) and
similar to that of normal adults, suggesting that the
trace amounts of HbF throughout adult life. Hemoglobin
hemoglobin switching had completed in these subjects.
can routinely be analyzed using chromatography or
Conversely, a significant increase in HbA2 and HbF levels
electrophoresis. Relative alterations of these hemoglobin
was observed in infants with heterozygous β-thalassemia
types have been shown to be associated with abnormal
and heterozygous HbE (Table 1). Te elevated HbA2
globin production in adults. For instance, hemoglobin
levels were similar to those of adults with heterozygous
E (HbE, α2β226Glu→Lys), the hallmark hemoglobinopathy
β-thalassemia. Regardless of age, this suggested that
of Southeast Asia, exists in a range from 25-90% of
increased HbA2 levels determine the inheritance of
the total hemoglobin in adults with HbE inheritance;
β-thalassemia. Interestingly, elevated HbF levels were
however, HbE levels present less than 25% of total
absent in adults with either heterozygous β-thalassemia
hemoglobin in heterozygous HbE patients who co-inherit
or heterozygous HbE,7,8 suggesting a developmental stage-
with α-thalassemia. Moreover, HbA2 is markedly raised
specific effect. Tis finding is comparable to previous
between 3.5 and 9.9% in adult heterozygous β-thalassemia.
studies in which the delayed HbF to HbA switching is
In contrast, relative changes in hemoglobin types are
remarkably shown in infants with β-globin defects.9,10
unnoticeable by routine hemoglobin analysis in adults
Although the mechanisms underlining HbF to HbA
with one or two α-globin gene defects.1 To broaden the
switching are unclear, the prolonged HbF levels in
knowledge and illustrate the effects of globin disorders
infants with a β-globin defect maybe due to the primary
on hemoglobin profile in infants, lefover blood samples
compensation of β-like globin gene expression and total
from 142 unrelated individuals aged between 8 and 12
hemoglobin during development in affected infants.
months with a mean corpuscular volume (MCV) less
Similar to those of adults with homozygous β0-thalassemia
than 80 fL were subjected to thalassemia screening and
and compound heterozygous β0-thalassemia with HbE
diagnosis. Hemoglobin analysis was performed regarding
disease, the increase in γ-globin gene expression has been
the Bio-Rad Variant II Hemoglobin Testing System with
shown to associate with milder clinical manifestations as
β-Talassemia Short Program (BioRad, Hercules, CA).
it is able to substitute for the inadequate β-globin gene
Te diagnosis of thalassemia was performed according
expression and yields increased HbF levels. In contrast
to standard diagnostic guidelines used in Tailand.2-4
to β-globin gene defects, heterozygous α0-thalassemia
In addition, common deletion types of α+-thalassemia
demonstrated comparable hemoglobin types to the
(-α3.7 and -α4.2) and α0-thalassemia (--SEA and --THAI)
normal in our finding. Despite insignificance, infants
were genotyped as described in previous studies.5,6 Te
with two α-globin gene defects displayed reduced HbA2
protocols in this study were approved by the ethics
and modestly increased HbF levels in the previous study.9
committee of the Faculty of Associated Medical Sciences,
Te decrease in HbA2 levels was clearly noticed in infants
Chiang Mai University, Chiang Mai, Tailand (ethical
with three α-globin gene defects or deletional HbH
approval reference number AMSEC-63EM-001). Te
disease in our study. Together, the results suggested that
results revealed that 59 (41.5%) were negative for the
HbA2 levels may be considered as valuable markers for
common thalassemias (hereafter so called normal),
the inheritance of globin gene defects in infants.
37 (26.1%) were heterozygous for β-thalassemia, 19
Volume 73, No.8: 2021 Siriraj Medical Journal
559
