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Homozygous
State
for
(Slow-moving
By Lie-Injo
Luan
Eng (Luan
Hb
Hb
Eng Lie-Injo).
Constant
X Components)
J. Ganesan,
A 12-yr-old
Malay boy who was studied because his youngest
brother
and
both
his
parents
had
the
slow-moving
Hb X
components
(earlier reported
to lead to Hb
H disease
when
combined
with
a-thaIassemia)
was found to be homozygous
for
the same slow-moving
components.
He had
splenomegaly
and a just palpable
liver, mild
anemia
with
microcytosis,
hypochromia,
slight morphologic
changes of the red blood
cells, and slight
reticulocytosis.
Of eight
children
in the family,
six had the trait for
the abnormality,
one was normal,
and one,
the propositus,
was homozygous.
Structural
studies of the isolated abnormal
hemoglobin
Spring
J.B.
showed
and
D.J. Weatherall
it to be identical
Spring
172
Clegg.
(Hb
CoSp),
residues
additional
minal
an
instead
31
end.
Hb
usual
attached
addition
to
Constant
variant
of the
being
In
to
a-chain
to
the
with
141,
the
the
C-ter-
abnormal
a
variant
for which
the
propositus
was
homozygous,
he also had normal Hb A and
normal
Hb A2 with normal a-chains.
If the
theory that Hb CoSp is due to a structural
mutation
affecting
the terminator
codon Is
correct, this case provides evidence for a duplication
of the gene for a-chain
production.
Results
of study
of several
erythrocyte
enzymes
are also reported.
H
EMOGLOBIN
H (Hb H) disease
in Malaysia
assumes
two forms,
one of
which
is associated
with slow-moving
hemoglobin
components
designated
Hb X. In those
subjects
with these
slow-moving
hemoglobin
components,
they
were invariably
found in one but not both ofthe
parents.”2
Hb
Slowly
migrating
H disease
in
significance
slow-moving
and mode
components
H disease
shown
end.5’6
family
structural
land,
and
Hb
components
Athens,3
of inheritance
were reported
designated
Hb
were reported
and in Thailand
were,
however,
in a Chinese
Constant
Spring
earlier
as
not
family
(Hb
in patients
Hb Thai4;
demonstrated.
from Jamaica
CoSp),
a variant
with
their
Similar
with Hb
which
was
to have abnormal
a-chains
with 31 additional
amino
acids at the C-terminal
The abnormal
slow-moving
hemoglobin
was also reported
in a Chinese
with Hb H disease
in the United
States,7
and in Hong
Kong.5
Subsequent
studies
on the slow-moving
hemoglobin
components
from Greece,
ThaiMalaysia,
and Hong
Kong
showed
them
to be identical
to Hb Constant
Spring
from
From
the
Francisco,
Lumpur.
Jamaica.9
University
Calif
Malaysia,
Submitted
August
hemoglobin
Greece
as
of
California
International
Center
for
Medical
(UC
Research
ICMR),
San
94143.
and the Division
of Hematology,
Institute
fi.sr Medical
Research,
Kuala
and the Department
of Hematology,
University
of Liverpool.
Liverpool.
England.
March
15,
1973:
first
revision
June
22,
1973,- second
revision
July
30,
1973:
accepted
from
the NIH
2. 1973.
Supported
by Research
Grant
HL-10486
and
by ICMR
M.D.,
Ph.D.,
Research
Grant
A 1-10051.
USPHS.
Lie-Injo
Luan
Eng
Health.
International
94143.
J. Ganesan,
Lumpur.
Malaysia.
England.
Di.
(‘enter
M.D.,
Eng
Lie-Injo),
for
Medical
D.C.P.:
J. B. Clegg, Ph.D.:
Weatherall,
Liverpool,
Liverpool.
1974 by Grune
Blood,
(Luan
M.D.,
England.
& Stratton,
Vol. 43. No. 2 (February).
Division
Research,
of
Hematology,
Department
F.R.C.P.,
D.T.M.
University
M.R.C.
Department
& H.:
of California,
Institute
of Hematologi.
Path.: Department
for
University
San
Medical
of International
Francisco,
Calif
Research,
Kuala
of Liverpool,
of Hematologi.
Liverpool.
University
of
Inc.
1974
251
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
252
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ENG
ET AL.
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
Hb CONSTANT
SPRING
Hb CoSp
were shown
253
in Malaysia,
to be identical
designated
slow-moving
to Hb CoSp,
occurred
Hb X components
in Kuala
Lumpur,
2.24%
of Malays,
0.66%
of Chinese,
and 0.16%
of Indians.’
were found
in certain
groups
of Malayan
aborigines.”
The
homozygous
condition
for these
Malay
boy was briefly
reported
the
clinical
and
hematologic
homozygous
Malay
boy. The
also reported.
slow-moving
by Lie-Injo.’2”
findings
and
results
of studies
MATERIALS
Hematologic
moglobin
Tris-boric
done
examinations
was done
acid
buffer
Rowe.”
boric
components
Alkali-resistant
structural
studies
ofthe
glutathione
activity
by
Valentine
were
quantitated
were
carried
Tanaka,22
and
and
by the
methemoglobin
Malay
X components
boy was studied
reductase
and
components.
2.
Hb
Bart’s
because
at
birth
in a
method
Singer
et
by the
level
of Beutler,2
(PK)
6.2.
Isolation
and
et al.
method
by the
of Zinkham
method
et
of Beutler
peroxidase
activity
by the method
at pH
of Marengo-
al.”
glutathione
kinase
was
buffer
by Clegg
estimated
activity
electrophoresis
electrophoretic
of
of he-
in discontinuous
in citrate
glutathione
pyruvate
8.0,
acetate
as described
was
method
Valentine,2’
8,6 and
Cellulose
method
out
activity
CASE
A 12-yr-old
the
Organization,”
activity
Paglia
7.7.
acetate
hemoglobin
(G6PD)
at pH
gel electrophoresis
by
(GR)
of
agar
by the cellulose
Health
found
Electrophoresis
buffer
at pH
and
estimated
World
reductase
acid
was
dehydrogenase
method
8.9,
X components
to standard
boric
buffer
at pH
frequencies
METHODS
according
phosphate
buffer
by the
the
and
and
acid
abnormal
as recommended
et al,,
9.5,
out
Higher
they
in
In this paper
we describe
in detail
the hemoglobin
analysis
in that
of several
erythrocyte
enzymes
are
AND
Tris-EDTA
hemoglobin
Glucose-6-phosphate
al.’
carried
gel using
at pH
in Tris-EDTA
Hemoglobin
were
on starch
Hb
before
Malaysia
by
the
of Hegesh
(GP)
method
of
et al.’
REPORT
his youngest
while
both
his
brother
was found
parents
had
the
to have slow-moving
same
Hb
slow-moving
Hb
X
3
The boy was well-nourished,
slightly small for his age, and was not jaundiced.
His spleen was slightly
enlarged and reached
two finger
breadths
below
the costal
margin
while his liver was just palpable.
No
other physical
abnormalities
were found.
He was examined
twice,
the second
time after the completion
of a course
was
first
of iron
Hematological
reduced
10-I
and
peculiar
the
small
started
Serum
iron,
serum
bilirubin
reacting.
and
pyruvate
Family
All
in the
to have
mild
listed
in Table
anemia
and
microcytosis
when
he
The
negative.
cells.
and
was
No
any
blood
target
erythrocytes
complete
at 0.20%
seen
could
and
and
there
Staining
decreased
slightly
anisocytosis
in addition,
with
be demonstrated.
at 0.40%
was
reticulocytosis.
slight
and,
a slightly
(control
level
a slight
be detected.
bodies
showed
was
showed
were
H inclusion
hemoglobin
There
smear
cells
normoblasts
Hb
I. The
reduced.
peripheral
I). A few
nor could
The
markedly
were
methyl
A sickling
osmotic
0.32%,
test
fragility:
respectively).
Coomb’s
test
activity,
negative.
of Zinkham
urine,
are
was
examined
but
in Table
the
dye
et al.,’7
was
bilirubin,
hemoglobin,
of glutathione
listed
Haptoglobin
by
peroxidase,
could
decoloration
not
be demonstrated
test
of
on starch
Motulsky
and
found
to be elevated.
Urobilin
and
and hemosiderin
were not detected.
glutathione
reductase,
gel
Campbellurobilinogen
The level
methemoglobin
of
reductase,
2.
Study
Both
parents
the
relatives
in Table
was
activities
kinase
was
(Fig.
shaped
bodies,
by the method
and
cells
Heinz
G6PD
glutathione
and
found
about
2 wk after completion
of an iron course,
was 89 .ig/ 100 ml (normal)
and
1.1 mg/lOO
ml total,
0.6 mg/lOO
ml direct
reacting,
and 0.5 mg/lOO
ml indirect
was
increased
are
MCH
normal.
blood
at 0.36%
direct
electrophoresis.
Kraut2’
he was
occasions
the
irregularly
examined
The
and
were
red
erythrocytes
hemolysis
were
because
both
ml,
counts
of the
violet did not reveal
of
on
I g/lO0
platelet
poikilocytosis
many
given
findings
at
WBC
therapy,
examined.
1. The
were
Malay.
were
healthy
father,
sister
They
and
No.
had
eight
without
2, and
children
physical
brothers
including
the
abnormalities:
Nos.
3 and
propositus
their
4 had
and
hematologic
microcytosis
his newborn
findings
of the
red
brother.
are
listed
blood
cells
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
254
LUAN
Fig.
1.
Peripheral
blood
cells; (B) Another
and
slight
shaped
anisocells.
cells,
and
The
although
they
within
family
of patient
had
and
normal
the
limits.
normal
in the
peripheral
grandmother,
and
MCV.
The
blood
sister
others
reticulocyte,
WBC,
Serum
iron levels
No.
did
and
are
El
for Hb CoSp. (A) A field showing
many small irregular shaped cells.
homozygous
blood smear showing
poikilocytosis
mother,
bodies were seen,
were
smear
field of patient’s
ENG
smears
I had
not
with
a few oval
similar
show
slight
significant
platelet
counts
listed
in Table
cells
changes
and
No
target
irregularly
of the
changes.
Hb
blood
red
H inclusion
were normal.
Serum
bilirubin
I. G6PD
activity
was normal
levels
in all
members.
Hemoglobin
Studies
On starch
hemoglobin
gel electrophoresis
a large
components,
moving
more
components
were
more
pronounced
usually
showed
could
be seen
drawn.
When
mobility
clearly
seen
two
of the
moving
clear,
and
when
the
examined
of Hb
in the
amount
slowly
of Hb A, a small amount
than
Hb A’,, were
found.
propositus
after
than those seen in the parents
only
globin
component
was not always
slow-moving
prepared
not
seen
time,
at the first
benzidine
instead
Hb A2 was
not always
hemolysate
for the second
Bart’s
than
was
with
and other siblings
components
slightly
faster
its appearance
freshly
staining
was
the patient
had
examination
a trace
on starch
(Fig.
of four.
on the
A2, and
of these
several
minor
slow-moving
2). They
the same
with
demonstrable
due to the
run
of Hb
Four
were
Sometimes
hemo-
(Fig.
3). This last component
hemolysate
being
old because
same
day
on which
of a hemoglobin
the
blood
component
gel electrophoresis
with
second
occasion,
Table
similar
2.
Hb
results
A2 1.8%,
were
obtained
of Sev.ral
Activity
of a Patient
combined
Homozygous
(Table
slow-moving
hemoglobin
I). In the parents
components
and
siblings
who
Quantitative
carried
Enzymes and Level of Glutathione
in Erythrocytes
for Hb CoSp and in those of His Parents
GR
U/gHb
withFAD
Patient
9.00
8.68
5.91
34
6.04
6.84
Mother
5.00
5.61
3.05
54
2.04
2.33
5.96
2.78
Father
5.11
5.06
3.16
51
3.60
4.23
4.27
3.06
6.56
6.18
1.80
60.08
3.50
5.95
3.34
1.80
1.43
0.36
12.82
1.12
1.10
0.64
values
PK
(U/1010R8C)
Glutathione
(mg/100miRBC)
GP
(U/gHb)
Methemoglobin
Reductase
(U/mgHb)
6PGD
(U/gHB)
Normal
on the
On
15.5
the
the ab-
G6PD
(U/gHb)
Subject
the
boric
5.2%.
A 93.0%,
it
was
in Tris-EDTA
first
Hb
who
another
results
occasion:
much
abnormality,
acid buffer at pH 8.6 and in phosphate
buffer at pH 7.7. No Hb H could be demonstrated.
analysis of hemoglobin
components
by cellulose acetate electrophoresis
gave the following
SD
AL.
3.41
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
Hb
CONSTANT
SPRING
255
.‘
0.
1’)
0
C,
C/)
0
C.)
C)
C.)
C)
c
Norrna
-
Control
-Ict.her
Patient
-
j
_Fth5’
Fig. 2.
Starch gel electrophoresis
in tris-EDTA-boric
acid buffer pH 8.6 showing
pattern
of the patient
and those of his parents.
The abnormal
components
are
nounced
in the patient
than in the parents
(benzidine
stain).
normal
X components,
between
0.5%
examination
normal
Four
I RC-50.6
earlier.”
and
and
limits
of the
2%
on
the
slow-moving
second
examination.
examined
(Table
on the
that
two
#{182}3 12
n
()
C.)
The
isolated
a-chains
of the components
12
levels
of
in the
level
the
patient
abnormal
was
found
of alkali-resistant
range
hemoglobin
to
to be 1 .3%
on the
hemoglobin
was
first
within
1).
were
abnormal
Ci:
13
I
showed
hemoglobin
components
studies
showed
analysis
Alkali-resistant
in all relatives
Structural
These
quantitative
1 .3%.
the hemoglobin
much
more pro-
and
purified
were
were
by chromatography
carried
identical
out
to the
according
Hb CoSpI
on
to methods
and
Amberlite
described
Hb CoSp2
frac-
C..
I
r_
r’j
-5
c
I
I
‘1other
Father
I--
Pti..nt
-i{b
A2
Indonesia
trait
+
Fig. 3.
Starch
gel electrophoresis
in discontinuous
tris-boric
acid buffer
pH 9.5 showing
the
hemoglobin
pattern
of the patient
and those of his parents,
compared
with those of normal
controls
and a control
Hb A2 Indonesia
trait carrier (benzidine
stain). CoSp4 is not visible in this picture.
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
256
LUAN
tiOns
Hb
Of
due
to
an
component.
was shown
minor
Constant
component
mobility
had
normal
which
A and
and
normal
(C-
There
abnormal
a-chains
attached
to
being
to a component
which
extended
to CoSp3
Hb
A, were
ti-chains,
were
in the abnormally
has
residues
corresponding
of [lb
chains.
those
31
which
corresponds
to have ,t-chains
the
normal
Spring.
additional
thus
no
slow-moving
172 residues
C-terminal
earlier
designated
to the Trp residue
in Fig.
isolated
while
with
the
2 was
and
not
The
abnormal
with
globin
hemoglobin
further.
Also,
hemoglobin
with
the
chains
instead
of the
mobility
in the
ofthe
AL.
141
A third
CoSp5
in Fig. 3,
chain.’
The fourth
the components
the
of the
with
mobility
of Hb A, had
blood
El
usual
a-chains.
CS3, but designated
I 54 of the a-CoSp
studied
analyzed.
the component
end
ENG
ofHb
normal
patients
A
a- and
other
than
components.
DISCUSSION
it
From
the clinical,
is clear
that the
CoSp.
definite
Although
clinical
hematologic,
and biochemical
patient
described
in this paper
he was discovered
and hematologic
pochromic
microcytic
although
mild, were
the peripheral
blood,
in the
were
trait
trait
be
and the family
homozygous
carriers
of
carriers
of
I-lb CoSp.
Hb CoSp
Several
of the
also had some
other
members
microcytosis,
No. 3 and
probably
findings,
changes
in
from those
of the family
hypochromia,
changes
of the red blood
cells (Table
1). The
No. 2 was accompanied
by normal
serum
iron
iron in brothers
No. 2 are therefore
studies,
for Hb
of a routine
family
study,
he had
He had splenomegaly
and hy-
anemia
even after
iron therapy.
The hematologic
clearly
abnormal,
with a reticulocytosis
and other
and the biochemical
findings
were quite different
slight
morphological
the father
and sister
serum
sister
only because
abnormalities.
findings
must
4 was low. The microcytosis
due to the presence
ofabnormal
who
and
microcytosis
levels while
in the father
Hb CoSp.
in
the
and
That
the microcytosis
and hypochromia
in brothers
No. 3 and 4 who had low serum
iron
levels were due or partly
due to iron deficiency
cannot
be excluded.
In a separate
study of many carriers
of Hb CoSp,
we have found
that the abnormal
hemoglobin
can
be accompanied
rocytes
The
although
amount
by slight
more often
of abnormal
microcytosis
found in the parents,
who were both trait
components
were easily
demonstrable.
derived
from
Hb CoSpl
by proteolysis,
produced
sometimes
components
hemoglobin
are
was
trace of Hb
Contrary
Bart’s was sometimes
to the usual finding
only about
5 of the
while a large amount
for a 1 variant
type
with
homozygous
the
propositus,
patient’s
of normal
Hb F often
of one known
who
morphologic
changes
total amount
I-lb A was
is obviously
cases
for an abnormal
of hemoglobin
found.
Usually,
or all the hemoglobin
present,
s-chain
but no
variant,
homozygous
genes controlling
would
not be the
pressor
tRNA
the structure
case,
however,
mutant,
which
of a-chains,
if Hb CoSp
was
suggested
is
Hb
the
for the
found
hemoglobin,
is of the
A. This
is also
Hb J Tongariki.25’2
abnormal
one normal
were due
as an unlikely
a
was of abnormal
type,
in a person
homozygous
Hb
abnormal
true
CoSp
normal
tv-chains,
also has at the same time normal
a-chains
in Hb A and
I-lb
CoSp
is due to a structural
mutation
affecting
the gene-terminating
which at present
is the most likely explanation,
the propositus
must have
of
that
The patient’s
level of alkali-resistant
between
normal
and abnormal,
and
detectable.
in homozygous
most
of the eryth-
unpublished).
to ten times
carriers
of Hb CoSp.
Also, four abnormal
Clegg
et al.” suggested
that
Hb CoSp
and it is likely
that the other
abnormal
in the same
way.
at the borderline
of hemoglobin
some
state
and
it is not (Lopez,
Lie-Injo,
and Lopes,
hemoglobin
in the patient
was five
for the
However,
with
ab-
Hb A2. If
codon,
two pairs
and one abnormal.
This
to the presence
of a supalternative
explanation
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
Hb CONSTANT
SPRING
for Hb CoSp.’
be duplicated
257
The suggestion
of Lehmann
has already
found
evidence
and Carrell27
in the reports
that the a-chain
gene may
of Brimhall
et al.2M and
Hollan
et al.,2
who described
two different
abnormal
types of a-chain
hemoglobin
in individuals
possessing
normal
‘Hb A as well. Assuming
theory
presents
of structural
mutation
is correct,
further
direct
evidence
for the
Further,
a certain
a-thalassemia
the severe
type,
production
Since
of
the
type
Hb
also
conclude
may
Q-a-thalassemia
from
(Hb
dude
that there is only
A in cases
homozygous
described
in the present
paper
of two a-chain
loci in Malays.
is thought
to be due
with
this
Q-H
that
Hb
one locus
for Hb
Hb
for a-chain
J Tongariki,
a-chains
are
A is present
gene
no Hb
to the combination
of
If the a-thalassemia
an a-chain
variant
normal
CoSp,
the a-chain
disease)
with
and
suppressed,
associated
of
the
the patient
existence
(Hb X components).’2’5”
that in a combination
A is completely
H disease
Hb
H disease
with Hb CoSp
it is expected
Hb
one
of Hb
variants
that
is duplicated.”4
found.
amounts
However,
A is found,#{176}32 and
in such cases.
an a-chain
not
in large
is of
the
one
has
in
to con-
Also, the absence
of Hb
variant
found
in Mela-
nesians,
leads
W the conclusion
that
the Melanesians
have
only
one
locus.2”’2t’
Since
both Hb H disease
with Hb CoSp
and Hb Q-a-thalassemia
in Chinese
it seems
possible
that both single
and duplicated
a-chain
loci
a-chain
occur
occur
in
this population,
provided
that the structural
mutation
theory
for Hb CoSp
is correct.
The newborn
brother
of the patient
had Hb CoSp
and Hb Bart’s in the blood.
As
reported
by Lie-Injo’3
Hb CoSp
(slow-moving
Hb X components)
in the newborn
is usually
accompanied
by Hb Bart’s.
In Malaysia
Hb Bart’s
in the newborn
does
not always
mean
company
different
which have
Erythrocyte
nothing
to do with
enzyme
studies
the activities
activity
Diaphorase
colytic
lation.
that the newborn
has
types ofabnormalities
of G6PD,
was
erythrocyte
As far
homozygous
PK,
and
because
a-, (3-, and
patient’s
GP
at the higher
limits
of
activity
was within
normal
enzymes
in the
Such an increase
and
a-thalassemia.’’”
showed
the
6PGD,
glutathione
to be very
normal
limits.
much
for
The
patient
was probably
was not found
in the
CoSp.
The low glutathione
due to increased
utilization
level
a-thalassemia,
involving
Hb Bart’s
can acrny-chain production,
level
to be low
elevated.
Also,
our
findings
in
increased
activity
due to a younger
parents,
who were
enzyme
activities
as we are aware
Hb CoSp
so
the
far
were
patient
reported.
reported
described
In the
in patients
in this
Temuan
paper
group
Malaysians.
of the gly-
erythrocyte
trait carriers
level and high GR activity
in the patient
of reduced
glutathione.
Similar
changes
and
the GR
popuof Hb
may have been
in glutathione
with
unstable
Hb
is the first case of
of Malayan
abo-
rigines
Hb CoSp
occurs
with a frequency
of 3.2%,”
so that it is to be expected
that
the
homozygous
condition
is not
very
rare.
A systematic
search
for such
homozygous
cases
among
the Temuan
has indeed
led to the finding
of another
family
with
three
members
homozygous
of the
room
for Hb CoSp.th
ACKNOWLEDGM
We thank
in collecting
patient
Kuala
the
blood
described
Lumpur,
staff
samples
in this
labor
from
paper:
for estimating
newborns
and
the
the bilirubin
of the
and
Division
and
ENT
Maternity
for
Unit
tracing
their
of Biochemistry
serum
iron
levels
General
relatives,
at the
in our
Hospital
which
Institute
patients
for their
generous
help
led to the
finding
of the
for
and
Medical
relatives.
Research,
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
LUAN
258
ENG
ET AL.
REFERENCES
I.
Lie-Injo
University
Medical
LE:
of California
Research
and
California,
GW
of
Acta
Wasi
P.
Sookanek
Ann
5.
NY
Acad
Milner
PI-.
variant
Lancet
1:729,
6.
with
JB,
Haemoglobin
Nature
Todd
9.
Clegg
10.
Lie-Injo
in
1971
of
haemoglobin
H
groups.
Duraisamy
X
Lancet
Hered
G:
22:118,
LI-,
slowin
Ma-
A,
(eds):
Constant
AN,
Spring
X components)
Am
Lie-Injo
Fourteenth
LI-:
Welch
hemoglobin
I Hum
Genet
S#{227}o
Paulo,
Lie-Injo
moving
hemoglobin
components
July
E in
reductase
(NA
a
(Basel)
49:25,
1973
14.
Dacie
IV:
Malay
I & A Churchill,
boy.
Practical
1968
I
KR:
on
the
of
Lab
Clin
1966,
AG,
vol.
IX.
New
M:
New
p468
N, Avron
reductase)
Med
72:339,
Campbell-Kraut
of the
red
the
lM:
cell,
and
Geographical
Grune
Popu-
dehydroin Blumberg
Conference
York,
in
1968
glucose-6-phosphate
of
ki-
Kaplan
ferrihemoglobin
Clin
of
deficiency
New
SP,
in I-nzymology,
Proceedings
Polymorphism
Pyruvate
DH-methemoglobin
genetics
Abramson
DC.
Saave
II:
dence
for
only
and
27.
in newborns.
Acta
Haematol
Haematology.
ER:
on
BS
Genetic
Variations
&
X
RK,
Stratton,
in
1961,
one
alpha
chain
Science
169:194,
GH,
Hornabrook
Occurrence
Shreffier
structural
in New
Evilocus
in
1970
RW,
of
for the a-chain
Lehmann
alpha-
H,
and
Fox
RH,
heterozygotes
and
haemoglobin
Guinea.
and
thalassaemia.
Possible
gene.
Br Med
Brimhall
B,
Carrell
variant
Nature
RW:
beta-chain
haemoglobin
28.
DL,
Hb I Tongariki:
(Lond)
1972
between
chain
Rucknagel
Homozygous
(Tongariki)
235:46,
slow.
slow-moving
Beaven
homozygotes
Hema-
Hb-J
Bart’s
the
Studies
in Colowick
determining
Motulsky
Huehns
H disease.
of
X components
for
Tanaka
Press,
I Lab
Melanesians.
25:382,
1972
Hemoglobin
state
in
of Hb
Congress
Brazil,
LI-:
homozygous
London,
aspects
stimsupple-
characterization
I-, Calmanovici
for
25.
(slow-moving
and
International
tology.
13.
New
WN,
aspects,
Hegesh
26.
12.
WN:
peroxidase.
Methods
Disease.
reductase:
1967
method
24.
glu-
by riboflavin
1969
Valentine
Academic
lation
Improved
blood
p159
Lewis
973
The
NO
BM:
1963
qualitative
glutathione
clinical
genase
1972
Baer
aborigines.
The
components
DE,
WHO
of
subjects
165:613,
Valentine
nase:
with
1958
for the study
Glutathione
and
erythrocytes.
5, Todd
Identification
racial
LI-,
Hemoglobin
Malayan
11:439.
I-:
70:158,
(ed):
Lie-lnjo
hemoglobin
bands
Na-Nakorn
Dl:
diflerent
Hum
II.
Med6l:882,
23.
Lancet
LI-,
haemoglobin
laysians.
I LahClin
York,
1971
Weatherall
from
and
hemoglobin-H
haemoglobin
haemoglohins
1972
QB:
50:1628,
I,
anomaly
and
Slow-moving
lB.
1:1308,
tathione.
22.
patients
102:169,
Kelly
determination
Med
Ortega
0,
I-, Duron
normal
Science
B:
l967
the
Huisman
C,
366,
for
Paglia
Childs
dehydrogenase.
Beutler
quantitative
Jr.
ofprocedures
No.
Beutler
denatu-
dehydro-
Hosp
19.
20.
RE,
from
Hopkins
method
erythrocyte
1971
RN,
hemoglobin
P. Lie-Injo
slow-mos’ing
moving
234:337,
termi
Lenhard
in erythrocytes
5cr
other
of alkali
glucose-fl-phosphate
.lohns
ulation
in
mentation.
PF:
chain
Hyman
disease.
Fessas
disease
(Lond)
Invest
in haemoglobin-H
Milner
Wrightstone
unusual
D:
Rep
demonand
1951
WH,
Standardization
Tech
L: Studies
Their
anemia
glucose-6-phosphate
Di:
haerno.
alpha-chain.
Dl,
to a-thalassaemia
J Clin
8.
Weatherall
to a unique
elongated
WA,
K: An
disease.
Bull
M,
in Thai-
Spring-a
GD,
its relation
activity
favism.
cellulose
Singer
1.
by means
Blood#{244}:4l3,
21.
Schroeder
Williams
D,
an
Constant
Efremov
THJ,
JB,
W!thll
mutant?
7.
5,
on
Al,
cell
disorders
genase
1971
Clegg
nation
Pootrakul
sickle
of
electrophoresis
1965
Chernoff
Zinkham
18.
1969
due
in
deficiency
of
165:60,
disease
glohin
of
P. Pornpatkul
Clegg
Haemoglobin-H
The
beta-thalessaemia
Sci
A
alpha.
18:790,
hemoglobins.
stration
Simultaneous
S.
K,
abnormal
17.
Society
an
Singer
Rapid
haemoglobins
Pathol
hematologic
p 56
Disthasongchan
and
an
of
I Clin
ration.
properties.
Na-Nakorn
M,
acetate.
Loukopoulos
International
1968,
V: Alpha-
land.
unusual
York,
new
1971
A,
Abstracts
New
A
“Athens”:
of the
M:
Al:
quantitation
16.
Lopes
disease.
Kaltsoya
with
Haematology.
Panich
H
Hemoglobin
Congress
4.
CG,
Marengo-Rowe
and
University
(Basel)46:l06,
K,
variant
Sessions.
.
Lopez
haemoglobin
P:
15.
the
Center
for
Francisco,
Foundation,
Haematol
Fessas
Twelfth
of
on
3. Sofroniadou
chain
International
Training,
San
LE,
lnheriance
D,
1970
17
Lie-Injo
aspect.
Report
Hooper
ofCalifornia,p
2.
Annual
between
of human
alpha-
duplication
I 4:748,
Differences
mutants
and
of
beta-
the
alpha-
RT,
Koler
1968
Holl#{225}n 5,
Jones
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
Hb
CONSTANT
RD,
chain
Stocklen
loci for
SPRING
259
Z, Szelenyi JO: Multiple
alphahuman
hemoglobin.
Clin
Res
Holl#{225}n SR.
Lie-Injo
cases
a-thalassemia).
18:184, 1970
29.
32.
Further
Szel#{233}nyi JG,
Brimhall
B,
Duerst
M, Jones
RT, Koler RD, Stocklen
Z:
Multiple
alpha
chain loci for human
haemoglobins:
Hb J-Buda
and Hb 0-Pest.
Nature
(Lond) 235:47, 1972
30. Vella F, Wells RHC, Ager JAM, Lehmann
H: A haemoglobinopathy
involving
haemoglobin
H and a new (Q) haemoglobin.
Br Med I 1:752,
1958
31. Lie-Injo
LE, Hart PL de V: Splenectomy
in two cases of haemoglobin
Q-H disease (Hb Qalpha-thalassaemia).
Acta
Haematol
(Basel)
29:358, 1963
33.
MedJ
34.
LE:
accompanying
Malaya
27:120,
Carrell
RW,
haemoglobin
6:116,
Pillay
Hb
Blood
Lie-Injo
ponents
LE,
of
haemolytic
RP,
Thuraisingham
disease
(Hb
Q-H
28:830,
Small
1966
haemoglobin
Hb
V:
Q-
Bart’s
in
comnewborns.
1972
Lehmann
anemia.
H:
The
Semin
unstable
Hematol
1969
35. Lie-Injo
LE, Lopez CG, Eapen IS, Eravelly I, Wiltshire
BG, Lehmann
H: Unstable
haemoglobin
K#{246}ln
disease in members
of a Malay
family. I Med Genet 9:340, 1972
36. Lie-Injo
LE, Welch QB, Ganesan
I: Three
members
of
a Malayan
aboriginal
family
homozygous
for
Hb
CoSp
(slow-moving
X
components).
(Manuscript
in preparation)
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
1974 43: 251-259
Homozygous State for Hb Constant Spring (Slow-moving Hb X
Components)
Lie-Injo Luan Eng, J. Ganesan, J. B. Clegg and D. J. Weatherall
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