Ann Hematol (2011) 90:123124

DOI 10.1007/s00277-010-0955-8

LETTER TO THE EDITOR

Mild hemoglobin H-constant spring disease

with -thalassemiaa case report
Dong-Zhi Li & Can Liao & Jian-Ying Zhou &
Xing-Mei Xie & Jian Li

Received: 10 March 2010 / Accepted: 23 March 2010 / Published online: 10 April 2010
# Springer-Verlag 2010

Dear Editor,
Thalassemia is one of the most common monogenic
diseases worldwide. In our area in the Guangdong province
of China, 8.53% of the population are -thalassemia
heterozygotes and 2.5% -thalassemia heterozygotes [1].
The co-inheritance of both - and -thalassemia is not
uncommon. However, the co-inheritance of hemoglobin
(Hb) H disease with heterozygous -thalassemia is rare.
Accurate diagnosis of these patients cannot be made from
Hb analysis alone. This study presents a family where the
interactions between - and -thalassemia compromised
the diagnosis of -thalassemia in the husband, which could
have resulted in a birth of -thalassemia major in the wife
who was a carrier of -thalassemia.
The couple screened positive for thalassemia during our
hospital-based prenatal screening program. This was their
first pregnancy. The wife had classical -thalassemia trait
(RBC 5.34 1012/L, Hb 108 g/L, MCV 67.6 fL, MCH
20.2 pg, Hb A 94.1%, Hb A2 5.0%, Hb F 0.9%). The
32-year-old husband presented red blood cell microcytosis
(RBC 5.02 1012/L, Hb 107 g/L, MCV 67.0 fL, MCH
21.1 pg), with the following characteristics of Hb analysis
by a capillary electrophoresis method (Sebia Capillarys 2
system): Hb A 93.6%, Hb A2 2.8%, Hb F 1.2%, Hb
D.-Z. Li : C. Liao : J.-Y. Zhou : X.-M. Xie : J. Li
Prenatal Diagnostic Center, Guangzhou Maternal & Neonatal
Hospital, Guangzhou Women & Children Medical Center,
Guangzhou Medical College,
Guangzhou, Guangdong, Peoples Republic of China
D.-Z. Li (*)
Prenatal Diagnostic Center,
Guangzhou Maternal & Neonatal Hospital,
Renminzhong Road 402,
Guangzhou, Guangdong 510180, Peoples Republic of China
e-mail: dongzhi3@yahoo.com.cn

Constant Spring (CS) 2.0%, and Hb Barts 0.4% (Fig. 1).

These findings did not suggest a diagnosis of Hb H-CS
disease, because the Hb H inclusion bodies were occasionally found, unlike that of other Hb H-CS disease patients in
whom there are generally a high proportion of Hb H
inclusion bodies, and there was also absence of the Hb H
band that characterizes Hb H disease. His medical history
was non-significant except a mild anemia. He had never
been transfused during his growth. His height was 160 cm
and his weight was 55 kg. The cardiovascular examination
was unremarkable. The abdomen was soft with no organomegaly. The serum ferritin level was in normal range.
Unexpectedly, -globin gene analysis confirmed the
genotype of SEA/CS in the husband, and the wife did
not co-inherit the -thalassemia. The fetus seemed to have
no chance of being affected with severe -thalassemia
syndrome. However, the mild clinical phenotype, the
reduced proportion of Hb H inclusion bodies, and the
absence of Hb H in the father still alerted us to the coinheritance of -thalassemia, although he had a normal Hb
A2 value. There were reports that co-inheritance of thalassemia trait in the Hb H disease could decrease the
level of excess -globin chains that could form Hb H and
inclusion bodies, resulting in less severe imbalance of /globin chain synthesis [2, 3]. Therefore, the Hb H level was
lower, there were fewer inclusion bodies, and the clinical
severity in the patients was greatly alleviated. As expected,
genotype analysis of -globin gene revealed that the
husband was a heterozygote for codons 4142 (-TCTT)
mutation, and the wife a heterozygote for IVS-II-654 (C>T)
mutation.
The clarification of the mutations in the parents made the
prenatal diagnosis possible. At 16 weeks of gestation,
amniocentesis was performed, and fetal DNA was extracted
from amniotic fluid. The genotype analysis disclosed that

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Ann Hematol (2011) 90:123124

heterozygous -thalassemia could show a normal level of

Hb A2, as described in this family. Definitive diagnosis of
concurrent Hb H disease and heterozygous -thalassemia
cannot be made from Hb analysis alone. Genotype
analysis therefore serves as an important diagnostic tool
to investigate patients with Hb H disease, especially when
accompanying with unexplained phenotypes.

Fig. 1 Hemoglobin analysis of the patient by capillary electrophoresis

References

the fetus had inherited both of the mutant alleles of the globin genes from the parents, and thus assumed to be a
homozygote for -thalassemia. The pregnancy was terminated at 18 weeks gestation.
The co-inheritance of both - and -thalassemia occurs
in areas with a high prevalence of globin gene mutations.
The chance of discovering co-existing -thalassemia in a
-thalassemia carrier depends on the individual's ethnic
background. This chance is relatively high in Southeast
Asia where 420% of the population are -thalassemia
carriers [47]. In our local practice, we do not routinely
determine the -thalassemia status in -thalassemia
carriers when the couple was discordant for thalassemia.
Although co-inheritance of -thalassemia can lead to a
reduction in the level of Hb A2, this does not interfere
with the diagnosis of -thalassemia carriers as the Hb A2
level in these double heterozygotes is still higher than the
normal level. However, concurrent Hb H disease and

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