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Genetic cholestasis: lessons from the molecular physiology of bile formation.
[benign recurrent intrahepatic cholestasis]
Progressive
familial
intrahepatic
cholestasis
(
PFIC
)
is
a
group
of
severe
genetic
cholestatic
liver
diseases
of
early
life
.
PFIC
types
1
and
2
are
characterized
by
cholestasis
and
a
low
to
normal
serum
gamma-glutamyltransferase
(
GGT
)
activity
,
whereas
in
PFIC
type
3
,
the
serum
GGT
activity
is
elevated
.
PFIC
types
1
and
2
occur
due
to
mutations
in
loci
at
chromosome
18
and
chromosome
2
,
respectively
.
The
pathophysiology
of
PFIC
type
1
is
not
well
understood
.
PFIC
types
2
and
3
are
caused
by
transport
defects
in
the
liver
affecting
the
hepatobiliary
secretion
of
bile
acids
and
phospholipids
,
respectively
.
Benign
recurrent
intrahepatic
cholestasis
(
BRIC
)
is
linked
to
a
mutation
in
the
same
familial
intrahepatic
cholestasis
1
locus
at
chromosome
18
.
Defects
of
bile
acid
synthesis
may
be
difficult
to
differentiate
from
these
transport
defects
.
Intrahepatic
cholestasis
of
pregnancy
(
ICP
)
appears
to
be
related
to
these
cholestatic
diseases
.
For
example
,
heterozygosity
in
families
with
PFIC
type
3
is
associated
with
ICP
,
but
ICP
has
also
been
reported
in
families
with
BRIC
.
In
Dubin-
Johnson
syndrome
there
is
no
cholestasis
;
only
the
hepatobiliary
transport
of
conjugated
bilirubin
is
affected
.
This
,
therefore
,
is
a
mild
disease
,
and
patients
have
a
normal
lifespan
.
Diseases
Validation
Diseases presenting
"transport defects in the liver affecting the hepatobiliary secretion of bile acids"
symptom
benign recurrent intrahepatic cholestasis
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