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Sapropterin dihydrochloride use in pregnant women with phenylketonuria: an interim report of the PKU MOMS sub-registry.
[phenylketonuria]
For
pregnant
women
with
phenylketonuria
(
PKU
)
,
maintaining
blood
phenylalanine
(
Phe
)
<
360
μmol
/
L
is
critical
due
to
the
toxicity
of
elevated
Phe
to
the
fetus
.
Sapropterin
dihydrochloride
(
sapropterin
)
lowers
blood
Phe
in
tetrahydrobiopterin
(
BH
4
)
responsive
patients
with
PKU
,
in
conjunction
with
a
Phe-
restricted
diet
,
but
clinical
evidence
supporting
its
use
during
pregnancy
is
limited
.
As
of
June
3
,
2013
,
the
Maternal
Phenylketonuria
Observational
Program
(
PKU
MOMS
)
sub-registry
contained
data
from
21
pregnancies
-
in
women
with
PKU
who
were
treated
with
sapropterin
either
before
(
N
=
5
)
or
during
(
N
=
16
)
pregnancy
.
Excluding
data
for
spontaneous
abortions
(
N
=
4
)
,
the
data
show
that
the
mean
of
median
blood
Phe
[
204
.
7
±
126
.
6
μmol
/
L
(
n
=
14
)
]
for
women
exposed
to
sapropterin
during
pregnancy
was
23
%
lower
,
and
had
a
58
%
smaller
standard
deviation
,
compared
to
blood
Phe
[
267
.
4
±
300
.
7
μmol
/
L
(
n
=
3
)
]
for
women
exposed
to
sapropterin
prior
to
pregnancy
.
Women
on
sapropterin
during
pregnancy
experienced
fewer
blood
Phe
values
above
the
recommended
360
μmol
/
L
threshold
.
When
median
blood
Phe
concentration
was
<
360
μmol
/
L
throughout
pregnancy
,
75
%
(
12
/
16
)
of
pregnancy
outcomes
were
normal
compared
to
40
%
(
2
/
5
)
when
median
blood
Phe
was
>
360
μmol
/
L
.
Severe
adverse
events
identified
by
the
investigators
as
possibly
related
to
sapropterin
use
were
premature
labor
(
N
=
1
)
and
spontaneous
abortion
(
N
=
1
)
for
the
women
and
hypophagia
for
the
offspring
[
premature
birth
(
35
w
4
d
)
,
N
=
1
]
.
One
congenital
malformation
(
cleft
palate
)
of
unknown
etiology
was
reported
as
unrelated
to
sapropterin
.
Although
there
is
limited
information
regarding
the
use
of
sapropterin
during
pregnancy
,
these
sub-registry
data
show
that
sapropterin
was
generally
well-tolerated
and
its
use
during
pregnancy
was
associated
with
lower
mean
blood
Phe
.
Because
the
teratogenicity
of
elevated
maternal
blood
Phe
is
without
question
,
sapropterin
should
be
considered
as
a
treatment
option
in
pregnant
women
with
PKU
who
can
not
achieve
recommended
ranges
of
blood
Phe
with
dietary
therapy
alone
.
Diseases
Validation
Diseases presenting
"restricted diet"
symptom
adrenomyeloneuropathy
classical phenylketonuria
lymphangioleiomyomatosis
phenylketonuria
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