Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
GM1-gangliosidosis in American black bears: clinical, pathological, biochemical and molecular genetic characterization.
[gm1 gangliosidosis]
G
(
M
1
)
-
gangliosidosis
is
a
rare
progressive
neurodegenerative
disorder
due
to
an
autosomal
recessively
inherited
deficiency
of
lysosomal
β-galactosidase
.
We
have
identified
seven
American
black
bears
(
Ursus
americanus
)
found
in
the
Northeast
United
States
suffering
from
G
(
M
1
)
-
gangliosidosis
.
This
report
describes
the
clinical
features
,
brain
MRI
,
and
morphologic
,
biochemical
and
molecular
genetic
findings
in
the
affected
bears
.
Brain
lipids
were
compared
with
those
in
the
brain
of
a
G
(
M
1
)
-
mouse
.
The
bears
presented
at
ages
10
-
14
months
in
poor
clinical
condition
,
lethargic
,
tremulous
and
ataxic
.
They
continued
to
decline
and
were
humanely
euthanized
.
The
T
(
2
)
-
weighted
MR
images
of
the
brain
of
one
bear
disclosed
white
matter
hyperintensity
.
Morphological
studies
of
the
brain
from
five
of
the
bears
revealed
enlarged
neurons
with
foamy
cytoplasm
containing
granules
.
Axonal
spheroids
were
present
in
white
matter
.
Electron
microscopic
examination
revealed
lamellated
membrane
structures
within
neurons
.
Cytoplasmic
vacuoles
were
found
in
the
liver
,
kidneys
and
chondrocytes
and
foamy
macrophages
within
the
lungs
.
Acid
β-galactosidase
activity
in
cultured
skin
fibroblasts
was
only
1
-
2
%
of
control
values
.
In
the
brain
,
ganglioside-bound
sialic
acid
was
increased
more
than
2
-
fold
with
G
(
M
1
)
-
ganglioside
predominating
.
G
(
A
1
)
content
was
also
increased
whereas
cerebrosides
and
sulfatides
were
markedly
decreased
.
The
distribution
of
gangliosides
was
similar
to
that
in
the
G
(
M
1
)
-
mouse
brain
,
but
the
loss
of
myelin
lipids
was
greater
in
the
brain
of
the
affected
bear
than
in
the
brain
of
the
G
(
M
1
)
mouse
.
Isolated
full-length
cDNA
of
the
black
bear
GLB
1
gene
revealed
86
%
homology
to
its
human
counterpart
in
nucleotide
sequence
and
82
%
in
amino
acid
sequence
.
GLB
1
cDNA
from
liver
tissue
of
an
affected
bear
contained
a
homozygous
recessive
T
(
1042
)
to
C
transition
inducing
a
Tyr
348
to
His
mutation
(
Y
348
H
)
within
a
highly
conserved
region
of
the
GLB
1
gene
.
The
coincidence
of
several
black
bears
with
G
(
M
1
)
-
gangliosidosis
in
the
same
geographic
area
suggests
increased
frequency
of
a
founder
mutation
in
this
animal
population
.