ACTA
MEDICA
PORTUGUESA
1985;
6:
137-141
ORIGINAL
RED
CELL
ABNORMALITIES
IN
A
KINDRED
WITH
AN
UNCOMMON
FORM
OF
HEREDITARY
SPHEROCYTOSIS
GABRIEL
OLIM,
SANDRA
MARQUES,
CARLOTA
SALDANHA,
DULCE
SANTOS,
PAULO
BARROCA,
J.
MARTINS
E
SILVA
Depa men
o
Biochemis y
-
Facul y
o
Medicine
and
Hema ology
Uni
-
Depa men
o
Medicine
III.
San a
Ma ia
Uni e si y
Hospi al.
Lisbon.
Po ugal.
SUMMARY
Red
cell
ace ylcholines e ase
(AChE)
and
Na,
+
K
~-
adenosine iphospha ase (ATPase)
ac i i ies,
cell
2,3
-
diphosphoglyce a e
(2,3
-
DPG)
and
adenosine iphospha e
(ATP)
con en
and
il e abili y
a io
we e
s udied
in
wo child en
(wi h
mode a e
hemoly ic
anemia and
ma ked
sphe ocy osis)
and
hei
pa en s.
Pa ien s’
pa en s
ha e no
medical
p oblem bu
e idenced disc e e
sphe ocy osis on
pe iphe al
smea .
Excep
some
inc eased
appa en
ed
cell
igidi y
de ec ed
in
he
a he ,
all
he pa ame e s
s udied
in
bo h
pa en s
we e
ound
o
be
no mal,
as
compa ed o
heal hy
con ols.
In
con as ,
ed
cell
igidi y,
2,3-DPG
and
ATP
le els
and
Na,
+
K
+
ATPase
ac i i y
we e
inc eased
in
bo h child en,
whe eas
AChE
ac i i y
was
simila
o
alues
o
no mal
subjec s.
These
obse a ions
sugges
ha bo h
a ec ed
pa ien s
su e ed
om
homozygous
he edi a y
sphe ocy osis
linked
o
an
appa en ly
ecessi ely
inhe i ed
ed
cell
memb ane
de ec .
RESUMO
Anomalias
e i oci ã ias
em
c iancas
po ado as
de
uma
a iedade
a a
de
es e oci ose
he edi ã ia
Em
duas
c iancas
(co n anemia
hemoli ica
mode ada
e
es e oci ose acen uada)
e
seus
pais
oi
de e mi
nada
a
ac i idade
da
ace ilcolines e ase
(AChE)
e
adenosino i os a ase
(ATP-ase)
-
Na,
+
K
+
-
-
dependen e
da
memb ana
e i oci á ia,
con eüdo
globula
em
2,3
-
di os oglice a o
(2,3
-
DPG)
e
adeno
sino i os a o
(ATP)
e
indice
de
il abilidade
e i oci ã ia.
Nenhum
dos
p ogeni o es
e idencia a
al e a
cOes
pa olôgicas
ou
ano nalias
naqueles
pa a ne os
labo a o iais,
além
da
es e oci ose
ligei a
em
ambos
e
aumen o
apa en e
da
igidez
globula
no
pai.
Pelo
con á io,
ambos
os doen es,
além
de
sinais
clinicos
ma cados,
e idencia am
il abilidade
e i oci á ia
nula
a
pa
do
aumen o
da
concen açAo
globula
do
2,3
-
DPG
e
ATP;
a
ac i idade
de
ATPase
Na,~
K
+
-
dependen e
e a
supe io
ao
no mal
apenas
em
u n
dos
doen es,
sendo
a
ac i idade
da
AChE
equi alen e
ados
con olos
no mais
em
ambos.
Os
esul ados
ob idos
pa ecem
e idencia
uma
o ma
a a
de
es e oci ose
he edi á ia
em
ambos
os
doen es
e en ualmen e
dependen e de
u n
de ei o
da
memb ana
he edi á ia
co n
ca ac e is icas
ecessi as.
INTRODUCTION
He edi a y
sphe ocy osis
(HS)
is
a
he e ogenous
diso
de ,
ei he
clinically
o in
e ms
o
he
molecula
de ec s,
in
appa en associa ion
wi h
a
p ima y abno mali y
o
he ed
cell
memb ane.”
2
Al hough
in
he
majo i y
o
he
cases
he
biochemical
de ec
is
s ill
unce ain,3
in
a
small
g oup
o
pa ien s
exhibi ing
ma ked
sphe ocy osis skele al
p o ein
changes
in ol ing
he
spec in molecule
ha e
been
desc ib
ed.4’
These
abno mali ies
migh
esul
in
memb ane
ins a
bili y,
ed
cell
agmen a ion
unde
ci cula o y
s ess
and/o
loss
o
e y h ocy e
de o mabili y.
The
inc eased
pe meabili y
o
sodium
(Na)
ions
obse ed
in
in ac
e y h ocy es
is
ano he
unc ional
de iciency
o
HS
cells,
pe haps
due o
s uc u al
changes
in
he
memb ane.6
In
addi ion
o
he
di e ences
epo ed
in
he
se e al
classes
o
ed
cell
memb ane
ATPase,7’
8
he e
is
also
some
e iden
ce
ha
he
p o ile
o
ace ylcholines e ase
(AChE) ac i i y
om
HS
pa ien s
is
clea ly
dis in
om
o he
hemoly ic
anemias.9
In
he p esen
pape
we
ocus
a en ion
on
ed
cell
mem
b ane
Na,
~
K
~
-
ATPase
and
ace ylcholines e ase
(AChE)
ac i i ies,
in
associa ion
o
he
index
o
e y h ocy e
il e abi
li y
(IF),
adenosine iphospha e
(ATP)
and
2,3
-
-
diphosphoglyce a e
(2,3
-
DPG)
concen a ions,
om
wo
siblings ( he
sons
o
ela ed
bu no mal
pa en s)
a ec ed
wi h
inhe i ed
sphe ocy osis.
Recei ed:
No embe
27,
1984
137
GABRIEL
OLIM
e
al.
MATERIAL
AND
METHODS
Case
epo s
and
ou ine
e alua ion
-
A
sugges i e
o m
o
he edi a y
sphe ocy osis
was
de ec ed
in
a
wel e-yea -old
whi e
boy
(pa ien
1)
i s
seen
by
us
o
clea
anemia,
skele
al abno mali ies
and
hepa osplenomegaly.
A
simila
clinical
si ua ion
was
soon
obse ed
in pa ien
2,
a
i e-yea -old
b o he
o
pa ien
1.
Bo h
pa ien s,
s ill
non-splenec omized
a
he
momen ,
showed
hemoly ic
anemia
cha ac e ized
by
hemoglobin
alues
anging
om
7
o
8
g/dl,
ele a ed
e icu
locy e
coun ,
sphe ocy es
on
pe iphe al
smea
and
mild
ele
a ion
o
unconjuga ed
bili ubin.
The
mos
impo an
ou i
ne
labo a o y
indings
o
bo h
siblings
and
hei
pa en s
( ou h
deg ee
cousins)
a e
summa ised
in
Table
1.
In
con as
wi h
he
physical
and
hema ologic
abno mali
ies
ound
in
bo h
siblings,
ei he pa en
has
had any
clinical
p oblem
and
bo h
had
no mal
physical
and
ou ine
labo a
o y
es s.
Howe e ,
a
small
pe cen age
o
sphe ocy es
as
well
as
poiquilocy es
and
inc eased
e iculocy e coun
(3-4,
5
Wo)
we e obse ed
in
blood
smea s
o
bo h
pa en s.
In
all
membe s
o
his
amily
he e
was
no
abno mal
hemoglobin
de ec ed,
HbA2
ande
HbF
le els we e
no
ais
ed,
Coombs’
es s
(di ec
and
indi ec )
we e
nega i e and
enzyme
ac i i ies
o
ed cell
py u a e-kinase
and glucose
6-phospha e
dehyd ogenase
we e
ound
o
be
compa able
o
hose
o
no mal
subjec s.
P ocedu es
-
Blood
om
each
pa ien
and
bo h
pa en s
was
d awn
in o
acu aine
ubes
con aining
hepa in
o
acid
ci a e
dex ose
as
an icoagulan s,
and
immedia ely
subdi i
ded
in
aliquo s
be o e
being
p ocessed
u he .
Red
cell
mo phology, blood
cell
coun s,
immedia e
osmo ic
agili y,
au ohemolysis
in
i o,
di ec
and
indi ec
Coombs’
es s,
hemoglobin
elec opho esis
and
o al
and
unconjuga ed
bili ubin
we e
pe o med
by
ou ine
labo a
o y
echniques.
Red
cell
2,3
-
diphosphoglyce a e
concen a ion
was
de
e mined
in
8
%
ichlo oace ic
acid
ex ac s
om
one
blood
aliquo ,
acco ding
o
he
me hod
o
Rose
and
Liebowi z.’°
The
e y h ocy e
adenosine iphospha e
con en
was
measu
ed
in
he
10%
pe chlo ic
acid
ex ac
o
each
blood
speci
men
by
he
me hod
o
Jawo ek
and
Cowo ke s.”
Red
cell
ace ylcholines e ase
ac i i y
was
measu ed
cob
ime ically
by
he
me hod
o
Kapland,’2
in
a
p epa ed
50%
suspension
h ee
imes saline-washed
e y h ocy es
and
using
ace yl hiocholine iodide
as
subs ac e.
Hemoglobin- ee
e y h ocy e
ghos s
we e
p epa ed by
hypo onic
lysis,
as
desc ibed
by
Cha
e
al.’3
P o ein
con en
was
measu ed
by
he
me hod
o
Low y.’4
Memb ane
Na,
+
K,
+
ATPase
ac i i y
was
de e mined
as
he
elease
o
ino
ganic
phospha e
du ing incuba ion
o
ghos s
wi h
ATP,
acco ding
o
he
echnique
o
Tausshy
e
al.’5
The
e y h ocy e
il e abili y
index
was
ca ied
ou
by
a
modi ica ion
o
he
me hod
o
Reid
e
al,’6
using
Nucleopo
e
polyca bona e
sie es
(Nucleopo e
Co p,
Pleasan on,
U.S.A.),
wi h
a
po e
diame e
o
5
/L;
e y h ocy es
suspend
ed
in
T is-albumin
bu e
(pH
7.4) a
a
hema oc i
o
8
%
we e
used
o
es ing
and
compa ed o
he
il a ion
ime
o
he
sol en ;
he
calcula ed
index
o
il a ion
inco po a ed
a
co ec ion
o
measu ed
hema oc j .’7
RESULTS
The
esul s
o
he ed
cell
s udied pa ame e s
in all
membe s
o
he
amily
a e
shown
in
Table
2.
Red
cell
AChE
ac i i y
o
pa ien s
and
hei
pa en s
ailed o
show
any
consis en
a ia ion
om
he
no mal
pa e n. Memb ane
Na,
+
K
+
-
ATPase
ac i i y
om
he pa en s showed
a
qui e
no mal
alue,
whe eas
aised
ac i i y
le els we e
ema kable
in hei
sons.
A
simila
ea u e
was
obse ed
wi h
TABLE
1
S anda d
hema ologic
da a
on membe s
o
he
amily
s udied
Pa ien Pa ien
2
Mo he
Fa he
Hemoglobin
(g/dl)
7.6
7.1
13.7 16.6
Hema oc i
(1/1)
0.22 0.22
0.45
0.52
Red
cell
coun
(x
10
12
/1)
2.7
2.6
5.0
5.6
Mean
co puscula olume
(I’l) 81.5
84.6
90.0 93.6
Mean
co pucula
hemoglobin
concen a ion
(g/dl)
34.5 32.3
30.4
31.7
Re iculocy es
(%)
7
18.5
3.5
4.2
Leucocy e
coun
(x
l0~
/1)
9.7 5.9
6.3
6.0
Pla ele coun
(x
10
9
/1) 300 360 300 280
To al
bili ubin
(mg/dl)
2.5
—
0.43
0.9
Unconjuga ed
bili ubin
(mg/dl)
1.9
— —
0.8
Se um
i on
(mg/dl)
87
128
141
121
To al i on
binding
capaci y
(mg/
dl)
187
— — —
Coombs
es s
(di ec
and
indi ec )
nega i e nega i e
—
—
Hemoglobin
F
(°lo)
2.5
2.0
—
—
Hemoglobin
A2
(%)
3.5
3.0
— —
Osmo ic
agili y
(g/l
NaC1)
hemolysis
begins
5.0
5.0
5.5
4.5
50%
hemolysis
(no mal
ange:
4.0-4.45)
4.65 4.45
4.35 4.15
Au ohemolysis
37°C
(%)
48
h,
wi hou
added
glucose
(no mal
ange:
0.2-4.5)
6.0 4.9
5.1
2.8
48
h,
wi h
added
glucose
(no mal
ange:
0-0.5)
1.21
0.95 0.73
0.80
Blood pe iphe al
smea
sphe ocy ic
RBC
+ +
+ +
nuclea ed
RBC
+
+
— —
poikilocy osis
and
agmen ed
RBC
+
+ +
+
anisocy osis
+ +
+ + +
÷
—
—
achan ocy ic
RBC
—
— —
Semi-quan i a i e
esul s
in
a
ange
o
0.4+;
RBC
ed
blood
cells.
138
HEREDITARY
SPHEROCYTOSIS
he
2,3
-
DPG concen a ion.
No
clea
a ia ion
on
ATP
le els
was
de ec ed
in
all
membe s
o
he
amily.
As
a
as
he
index
o
ed
cell
il a ion
is
conce ned,
he inc eased
alues
obse ed
in
bo h
pa ien s
and,
also
in
hei
a he ,
migh
indica e
a
loss
o
de o mabili y,
in
con as
o
he
no mal
alue de ec ed
in
he
mo he .
DISCUSSION
He edi a y
sphe ocy osis
seems
o
be
he
esul
o
s uc
u al
de ec
o
e y h ocy e
memb ane,
ye
o
be
de ined
in
he
mos
equen
o m.
1-3
Usually
his
diso de
occu s
wi h
disc ee
clinical
symp oms
and
mild
anaemia,
in appa en
dependence
o
a
mendelian
au osomal
ai ,
pe haps
wi h
a iable
pene ance;
no
cases
o
homozygo y
ha e
been
desc ibed.’8’
19
The
p esence
o
sphe ocy ic
cells
in all
membe s
o
he
amily
we
ha e
s udied
appea s
as
an
uncommon
e en .
Al hough
no
clinical
mani es a ions
we e
appa en
in
he
(dis an ly
ela ed)
pa ien s’
pa en s,
mild
sphe ocy osis and
o he
signs
o
p esumed
hemoly ic
compensa ion
we e
de ec ed
on
blood
smea .
In
con as ,
bo h
siblings
showed
ema kable
sphe ocy osis
and
o he
ed cell
abno mali ies
(Table
1),
in
associa ion
wi h
clea
clinical
symp oma ology.
The
ob ious
poikilocy osis
and he
no mal
alues
o
mean
co puscula
hemoglobin
concen a ion,
as
obse ed
on
hese
cases,
a e
unusual
labo a o y
e en s
in
HS.
Al
hough
some
con usion
may
a ise
wi h
o he
sphe ocy ic
hemoly ic
anemias,
i
is
unsa e
o
assume
ha
one
is
no
dealing
wi h
HS.
In
ac ,
he
combina ion
o
anemia,
inc eas
ed
e iculocy osis
(pa icula ly
e iden in
pa ien
2),
sligh
ele a ion
o
se um-indi ec
eac ing
bili ubin
(in
pa ien
1),
sphe ocy osis,
osmo ic
agili y
(in pa ien
1),
au ohemolysis
(in
bo h),
splenomegaly
and
skele on
abno mali ies,
as
obse ed,
suppo
he diagnosis
o
HS.
Meanwhile,
he
epo ed
nega i e
Coombs’
es
and
co
ec ed
au ohemolysis
by
glucose excludes
he
diagnosis
o
immune
sphe ocy osis;
he
di e en ia ion
om
he
a ious
causes
o
splenomegaly
and
hype splenism
o e ed
no
doub
by
he
physical
examina ion;
he
inexis ence
o
ed
cell
glucose
6-phospha e
dehyd ogenase and
py u a e-kinase
de iciencies,
o
he
absence
o
sickle cell
ai
and
o he
he
moglobinopa hies
also
dis inguished
he
p esen ing
cases
om
congeni al
non-sphe ocy ic
hemoly ic
anemias.
Such
appea ance
may
sugges
ha
he
pa ien s
a e
ho
mozygous
o
a
ecessi e
ai ,
esponsible
o
a
congeni al
hemoly ic
anemia
wi h
he
main
cha ac e is ics
o
he edi a y
sphe ocy osis.
In
addi ion,
bo h
pa ien s
clea ly
exhibi ed
dec eased
e y h ocy e
de o mabili y,
also
obse ed
in
a
sligh es
de
g ee
in
hei a he .
The
educed
de o mabili y, docummen
ed
by
a ious
me hods
as
a
cha ac e is ic
abno mali y
o
HS
e y h ocy es,2°
migh
be
in
he
p esen ing
cases
a
conse
quence
o
diminished
su ace
a ea/ olume
a io21
and
/
o
educed
mechanical
s abili y
o
sphe ocy ic
memb anes.22
As
a
consequence
o
a
educed
de o mabili y, p og es
si e
memb ane
loss
and cell
agmen a ion
occu s
in
he
ci cula ion
and
migh
be
ela ed
o
he
se e i y
o
hemolysis
and
esul ing
anemia
in
HS
pa ien s.’9’2°
In
ac ,
he
abno
mal
osmo ic
p ope ies
23
and
dec eased
li espan
o
HS
e y h ocy es
21
ha e
been
a ibu ed
o
a
diminished
su ace
a ea/ olume a io
23
also
sugges ed
as
he
p ima y ac o
leading
o
dec eased
de o mabili y.
In addi ion,
he educed
su ace
a ea/
olume
a io
appea s
o
be
co ela ed
‘wi h
he
deg ee
o
sphe ocy e
igidi y.24
Al hough
ou
pa ien s’
pa en s
also p esen ed
sphe ocy
ic
cells,
he pe cen age
o
hei
expec ed
unde o mable
cells
was
no
su icien
o
p oduce
he
hema ologic
pa e n
o
ypical
HS,
bu
a
disc ee
educed
e y h ocy e
de o mabili y
in
he
a he .
Fo
he
majo i y
o
HS
pa ien s,
he
ed
cells
ha e
a
no
mal
discocy ic
shape
and
abou
no mal
osmo ic
and
mem
b ane
p ope ies;
only
a
a iable
subpopula ion
o
uly
sphe ocy ic
cells
accoun s
o
he
di e ence
in
de o mabili y
and he
deg ee
o
he
anemia.24
So
a ,
he
mode a e
ane
mia
and
osmo ic
agili y
showed
in
bo h
siblings
migh
be
explained
by
a
ema kable
pe cen age
o
unde o mable
sphe ocy es,
as
obse ed.
As
a
likely
consequence
o
he
ed
cell
agmen a ion,
he
inc eased
2,3
-
DPG
con en
ound
in
bo h
pa ien s
could
accoun
o
educed oxygen
a ini y
o
hemoglobin25
and
hence
mo e
oxygen
being
eleased
o
he
hypoxic
issues.26
Ou
da a
oppose
o me
esul s
o
low
2,3
-
DPG
le els
in
HS
pa ien s,
also
wi h
in ac
spleen,27
bu
a e
in
ag eemen
wi h
mo e
ecen esul s
o
inc eased ed cell
2,3
-
DPG
con en in
HS
child en.28
The
al e a ion
in
ed
cell
2,3
-
DPG
le els
migh
be
also
go e ned
by
some
o he
me abolic ac o s,
namely
he
o e
all
a e
o
e y h ocy e
glycoly ic
pa hway.29
Al hough
he
a e
o
glycolysis
is
dec eased
in
human
e y h ocy es
con aining
high concen a ions
o
2,3
-
DPG
unde in
i o
condi ions,29
he
concen a ion
o
ATP
we e
ound
o
be
sligh ly
ele a ed
in
high
DPG
cells.30
Fu he
mo e
he e
is
no
e idence
o
a
majo
dec ease
in
he
le els
o
ATP
when
2,3
-
DPG
concen a ion
inc eases
in
a ious
hypoxic
condi ions
•31
The
majo
ca ion
lux
abno mali y
in
HS
cells
appea s
o
be
an
excessi e
sodium pe meabili y.6
HS
cells
oppose
he
TABLE
2
Red
cell
2,3-diphosphoglyce a e
and
adenosine iphospha e
concen a ion,
il e abili y
a io,
memb ane ace ylcholines e ase
and
Na,
~
K
-
adenosine iphospha e ac i i ies
No mal
con ols
Pa ien
I
Pa ien
2
Mo he
Fa he
(mean;
SD)
2,3
-
diphosphoglyce a e (1 moles/gHb)
18.4
21.6
11.6
12.5
12.5;
1.8
Adenosine iphospha e
(~smoles/gHb)
6.7
5.5
4.4
3.8
5.9;
1.1
Fil e abili y
a io
no
il a ion
12.2
34.4
13.9;
2.2
Ace ylcholines e ase
(U/min/mgHb)
232
230
229 280
231.7;
52.5
Na,
+
K
+
-
ATPase
(jhmoles
phospha e/mg
memb ane
p o ein)
0.316
0.548
0.109
0.144
0.160;
0.085
139
GABRIEL
OLIM
e
a!.
abno maly high Na~
in lux
by
inc eased
pumping,
depen
den
o
highe
ATP
gene a ion
by
glycolysis.32’
~
The
highe
han
no mal
Na,
+K~
ATPase
ac i i y
obse ed
in
bo h
siblings,
con i ming o me
s udies
in
HS
pa ien s,7’33
could
be
a
e lec ion
o
an
excessi e
sodium
pe meabili y
in
HS
cells,
being he
Na~
pumping
sus ained
by
inc ease
glycoly
sis;
hus
an
ele a ion
in
ATP
le els
(wi h
pa allel
inc ease
o
2,3
-
DPG)
migh
be
equi ed
o
main ain
he
ion
pumping.
Howe e ,
such
gain
in
in acellula
ATP
was
no
e iden
in
ou
s udy,
and
seems
dissocia ed
o
inc eased
2,3
-
DPG
le els.
In
HS
cells,
he
Na,~
K~
-
ATPase
was
shown
in
co e
la ion
wi h
he
a e
o
sodium
e lux;33
howe e ,
none
o
hese
pa ame e s
seems
o in luence
he ed
cell
su i al.34
In addi ion,
nei he
he HS
cells
became
sphe ical
due
o
an
inc ease
in
o al
ca ion
and
wa e
con en 23
no
he
sphe oi
dal
shape
i sel
is
esponsible
o
inc eased glycolysis;35
simila
abno mali ies
in
ca ion
lux
and
pumping
a e
also
ound
in
some
o he
hemoly ic
36
o
nonhemoly ic
diso de s.
~
All
hese
obse a ions
sugges
ha
excessi e
sodium
pe
meabili y
and
e y h ocy e me abolic
adap a ion,
as
well
as
some
o he
desc ibed
cha ac e is ics
o
HS
cells
(e.
g.
sphe
odici y,
inc eased
osmo ic
agili y,
changes
in
memb ane
lipids
o
abno mali ies
in
memb ane
p o eins
and
lipid
phospho yla ion)
a e
seconda y
o
basic
s uc u al
changes
in
ed cell
memb ane.
1-3,
19,
20,
37
This
iew
seems
o
be
also
pa ly
suppo ed
in
a
ecen
s udy,
whe e
he
p o ile
o
e y h ocy e
memb ane
ace yl
cholines e ase
in
HS
was
clea ly
dis in
o
no mal
and
some
o he
hemoly ic
anemias;9
he
ele a ion
o
AChE
ac i i y
was
de ec ed
exclusi ely by
using
an
ionic
subs ac e and
was
inappa en
wi h
a
lipophylic
one,
pe haps
due
o
a
mo e
ully
exposi ion
o
he enzyme molecules a he
ou e
memb ane
side;
howe e
he
AChE
ac i i y
was
no
in luenced
by
he
sphe ocy ic
shape.
Con e sely,
we
we e
unable
o
con i m
by
simila
me ho
dology
an
ele a ion
o
e y h ocy e
AChE
ac i i y
in ou
pa ien s
o hei
pa en s.
This
disc epancy
be ween
ou
esul s
and
hose
o
S eichman
e
a19
may
be
due
o
changes
ha
pa icula
cy oskele al
memb ane
in e ac ions
may
impose
o
he
AChE
molecules,
in
dependence
o
he
ansmemb a
ne
con ol
o
in eg al
memb ane
p o ein
dis ibu ion.38
In
spi e
o
all
sphe ocy osis
is
no
he
same,
13,
18,
19
and
he
unde lying
molecula
abno mali y
is
s ill
unde inied
o
he
majo i y
o
HS
pa ien s,39
mos
da a
poin
owa ds
he
ed cell
memb ane
cy oskele on
as
being
he
si e
o
he
p ima y
gene ic
de ec
in
HS.
In
his
ega d
and
associa ed
o
he
he e ogenei y
in
inhe i ance,
he
basic
lesion
in
HS
migh
e lec
di e se
ab
no mali ies
o
he
memb ane
cy oskele on,
pe haps
as
inal
consequence
o
many
dis inc
biochemical
de ec s,
as
e
cen ly
sugges ed.40
The
clinical
cou se
and
uncommon
inhe i ance
pa e n
o
ou
pa ien s may
be
ela ed
o
a
such
s ill
unco e ed
mem
b ane de ec .
Fu he
in es iga ions
upon
he ed
cell
mem
b ane
cha ac e is ics
in
his
amily
a e
now
in
p og ess
in
ou
labo a o y.
ACKNOWLEDGMENTS
This
s udy
was
suppo ed
in
pa
by
a
g an
om
INIC
(MbL2).
The
echnical
assis ance
o
M .
Chim
W.
San
is
g a e ully
acknowledged. The
au ho s
also
hank
Miss
Emi
ha
Al es
o
yping
he
manusc ip .
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