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Globotriaosylsphingosine (lyso-Gb3) might not be a reliable marker for monitoring the long-term therapeutic outcomes of enzyme replacement therapy for late-onset Fabry patients with the Chinese hotspot mutation (IVS4+919G>A).
[fabry disease]
In
Taiwan
,
DNA-based
newborn
screening
showed
a
surprisingly
high
incidence
(
1
/
875
in
males
and
1
/
399
in
females
)
of
a
cardiac
Fabry
mutation
(
IVS
4
 
+
 
919
G
 
>
 
A
)
.
However
,
the
natural
course
,
long
-term
treatment
outcomes
and
suitable
biomarkers
for
monitoring
the
therapeutic
outcomes
of
these
patients
are
largely
unknown
.
Fabry
disease
(
FD
)
patients
who
had
received
enzyme
replacement
therapy
(
ERT
)
for
more
than
1
Â
year
were
enrolled
in
this
study
from
December
2008
to
April
2013
.
Periodic
echocardiography
and
serum
globotriaosylsphingosine
(
lyso-
Gb
3
)
analysis
were
carried
out
.
Before
and
after
ERT
,
left
ventricular
mass
index
(
LVMI
)
and
serum
lyso-
Gb
3
level
were
compared
and
the
correlation
between
the
change
of
LVMI
and
the
change
of
serum
lyso-
Gb
3
were
also
analyzed
.
Thirty
-
six
patients
,
in
four
patient
groups
,
were
enrolled
:
(
1
)
16
males
with
IVS
4
 
+
 
919
G
 
>
 
A
mutation
;
(
2
)
7
females
with
IVS
4
 
+
 
919
G
 
>
 
A
mutation
;
(
3
)
2
males
with
classical
mutations
;
and
(
4
)
11
females
with
classical
mutations
.
The
follow-up
period
was
13
-
46
months
.
There
were
significant
LVMI
reductions
after
ERT
in
all
four
groups
after
excluding
confounding
factors
.
However
,
interestingly
,
serum
lyso-
Gb
3
decreased
significantly
in
the
early
period
after
ERT
in
all
groups
,
but
increased
gradually
after
an
average
of
11
.
1
Â
months
after
ERT
in
late-onset
male
and
female
Fabry
groups
,
even
when
their
LVMI
still
decreased
or
remained
stable
.
Furthermore
,
there
was
no
correlation
between
the
change
of
serum
lyso-
Gb
3
and
the
change
of
LVMI
in
both
classical
and
IVS
4
 
+
 
919
G
 
>
 
A
FD
patients
.
Although
lyso-
Gb
3
has
a
high
diagnostic
sensitivity
in
late-onset
Fabry
patients
and
has
a
good
response
to
ERT
during
the
early
stages
,
it
might
not
be
a
reliable
marker
for
monitoring
the
long
-term
therapeutic
outcomes
of
ERT
for
late-onset
Fabry
patients
with
the
Chinese
hotspot
mutation
(
IVS
4
 
+
 
919
G
 
>
 
A
)
.
Diseases
Validation
Diseases presenting
"change of serum lyso-gb3"
symptom
fabry disease
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