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Is subclinical adrenal failure in adrenoleukodystrophy/adrenomyeloneuropathy reversible?
[adrenomyeloneuropathy]
X-
linked
adrenoleukodystrophy
/
adrenomieloneuropathy
(
ALD
/
AMN
)
is
a
progressive
neurodegenerative
disorder
due
to
mutations
in
the
ABCD
1
gene
encoding
the
ABC
transporter
ALDP
.
Mutations
in
ALDP
impair
peroxisomal
β-oxidation
of
very
long
chain
fatty
acids
(
VLCFA
)
,
resulting
in
elevated
levels
of
VLCFA
in
plasma
,
nervous
system
,
and
adrenals
.
Lorenzo
's
oil
,
combined
with
VLCFA-
poor
diet
,
normalizes
plasma
VLCFA
within
1
month
,
but
it
does
not
prevent
the
progression
of
pre-existing
neurological
symptoms
.
No
previous
study
analyzed
the
effect
of
Lorenzo
's
oil
therapy
on
adrenal
function
.
To
investigate
short
-term
effects
of
Lorenzo
's
oil
,
combined
with
VLCFA-
poor
diet
,
on
adrenal
function
of
AMN
patients
with
early
subclinical
signs
of
adrenal
failure
.
Seven
AMN
subjects
underwent
VLCFA-
restricted
diet
combined
with
Lorenzo
's
oil
(
45
ml
/
day
po
)
,
without
steroid
therapy
,
for
6
months
.
All
patients
had
elevated
ACTH
at
baseline
,
and
a
significant
reduction
was
evident
after
6
months
(
median
ACTH
at
baseline
:
1300
pg
/
ml
,
range
:
720
-
2100
;
median
ACTH
at
6
months
:
186
pg
/
ml
,
range
:
109
-
320
,
p
:
0
.
0156
)
.
Cortisol
was
normal
both
at
baseline
and
after
6
months
.
VLCFA
dropped
in
all
patients
during
the
6
-
month
follow-up
,
and
no
patient
required
glucocorticoid
replacement
therapy
.
Adrenal
insufficiency
in
ALD
/
AMN
is
probably
due
to
a
defective
adrenal
response
to
ACTH
,
related
to
VLCFA
accumulation
with
progressive
disruption
of
the
adrenal
cell
membrane
functions
.
In
an
early
phase
,
Lorenzo
's
oil
therapy
may
be
able
to
improve
VLCFA
clearance
and
restore
a
normal
ACTH
receptor
activity
,
and
hypoadrenalism
may
be
potentially
reversible
.
Diseases
Validation
Diseases presenting
"restricted diet"
symptom
adrenomyeloneuropathy
classical phenylketonuria
lymphangioleiomyomatosis
phenylketonuria
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