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| Schipperke
Health |
| Genetic Disorder -
MPS IIIB |
Note
Update:
SCA
Health
and
Genetics
Committee
re
MPSIIIB
(10/31/04)
There
have
been
a
few
errors
in
test
results.
They
are
most
probably
due
to
human
error
on
the
part
of
either
the
sample
gatherer
or
the
lab,
but
we
can
not
pin
point
where
the
problem
was.
The
test
itself
is
very
accurate.
That
being
said
we
would
recommend:
All
breeding
animals
should
be
tested.
Do
not
rely
on
normal
by
pedigree.
If
you
are
breeding
known
carriers:
Normal
dogs
bred
to
carriers
should
be
retested
to
be
sure
they
are
normal.
Puppies
from
known
carriers
should
be
tested.
If
anyone
notices
discrepancies
in
their
test
results,
it
would
help
if
you
would
send
details
to
Shirley
Quillen,
Chairman
of
the
Health
and
Genetics
Committee
at
imaskip@earthlink.net
. |
|
|
Mucopolysaccharidosis
type IIIB
(MPS IIIB)
in Schipperkes
and DNA
testing
This
recently
identified
genetic
disease
is present
in Schipperkes
and in
humans.
When a
dog is
affected
it is
ultimately
lethal.
The gene
has been
identified
in many
of our
dogs in
the current
population.
It is
imperative
that we
learn
about
this disease
and test
all dogs
prior
to using
them for
breeding
from this
point
forward.
Read the
information
below
furnished
by Dr.
Ellinwood,
the researcher
studying
this disease.
For testing and submission information:
http://research.vet.upenn.edu/penngen and also the PennGen submission database https://netapps.vet.upenn.edu/PennGen/SampleTesting/default.aspx
It is
by permission
of and
request
from the
researcher
Dr. Matthew
Ellinwood
that this
information
be widely
disseminated
among
Schipperke
fanciers
and breeders.
If you
are a
breeder
and find
that you
have an
unplaced
affected
pup, or
if you
are an
owner
of an
affected
dog, and
you would
like to
know how
you can
help to
further
efforts
to find
a treatment
and a
cure for
this devastating
disease,
we encourage
you to
contact
penngen@vet.upenn.edu
Summary
Detail
|
Summary:
What
is
Mucopolysaccharidosis
type
IIIB
(MPS
IIIB).
The
disease
MPS
IIIB,
also
known
as
Sanfilippo
syndrome
type
IIIB,
is
an
inherited
disease
classified
as
a
lysosomal
storage
disease
(LSD).
Lysosomes
are
"bags"
within
cells
of
the
body,
filled
with
special
enzymes
which
disassemble
molecules
in
an
orderly
manner.
If
one
of
the
enzymes
is
missing,
due
to
mutations
in
the
gene
for
that
enzyme,
the
disassembly
stops,
and
undegraded
molecules
accumulate
in
lysosomes
(hence
the
term
LSD),
and
the
cells
become
sick
or
die,
which
leads
to
disease.
The
compound
accumulating
in
MPS
IIIB
is
heparan
sulfate
and
the
affected
enzyme
is
N-acetyl-a-D-glucoseaminidase
(NAGLU).
What
are
the
symptoms
of
MPS
IIIB.
The
clinical
signs
in
the
dogs
are
related
to
brain
disease,
appear
between
2-4
years
of
age,
and
include
tremor,
and
difficulty
in
balancing,
walking,
and
negotiating
obstacles
such
as
stairs.
The
disease
is
progressive,
and
owners
have
chosen
euthanasia,
usually
1-2
years
after
recognizing
clinical
signs.
How
is
MPS
IIIB
inherited?
The
inheritance
pattern
of
MPS
IIIB
is
autosomal
recessive.
Both
males
and
females
are
equally
capable
of
having
the
disease,
or
of
being
carriers.
Carriers
are
absolutely
normal,
and
will
not
have
signs
of
the
disease.
Is
there
a
DNA
test
and
if
so
what
do
the
DNA
test
results
mean?.
We
have
a
mutation
based
test
for
the
NAGLU
mutation
in
the
Schipperke
breed.
Testing
offered
through
at
the
University
of
Pennsylvania
reports
a
result
of
affected,
carrier,
or
normal.
How
do
I
go
about
getting
my
dog
tested?
See
the
submission
form,
and
attached
instructions
and
check
list.
Who
receives
notification
of
the
DNA
test
results?
Results
are
confidential
and
are
released
only
to
the
individual
that
submitted
the
sample.
How
common
is
this
disease
and
how
long
has
it
been
in
the
Schipperke
breed?
The
mutant
gene
may
be
as
far
back
as
eleven
generations,
and
hence
may
be
very
broadly
distributed
in
the
Schipperke
population.
The
carrier
frequency
is
unknown,
but
judging
from
similar
diseases
in
cattle,
it
may
be
as
high
as
15%.
If
the
mutation
is
so
old,
why
has
this
not
been
seen
before?
Probably
this
disease
has
been
seen
before,
but
was
not
recognized.
Factors
contributing
to
this
including
a
low
frequency
of
cases,
non-specific
clinical
signs,
an
adult
onset,
a
lack
of
post-mortem
examinations,
and
very
limited
knowledge
among
medical
professionals.
Who
should
have
their
animals
tested?
Every
breeding
animal
should
be
DNA
tested
for
this
disease.
All
pups
that
are
waiting
to
be
placed
in
permanent
homes
should
be
considered
for
testing,
to
spare
their
new
owners
a
great
deal
of
anguish
and
anxiety.
What
do
I
do
if
I
have
pups
waiting
to
go
to
homes?
Priority
testing
to
ensure
that
pups
waiting
for
placement
are
not
affected
will
be
made.
See
the
details
below.
Do
we
provide
"rush"
testing
on
samples,
bulk
prices
or
special
litter
prices?
Rush
testing
is
not
available.
There
are
also
no
bulk
submission
or
litter
submission
price
adjustments.
What
samples
is
the
test
run
on?
The
test
can
be
run
on
either
1-2
ml
of
EDTA
blood
(lavender
topped
tube),
or
on
cheek
swabs.
Detail:
What
is
MPS
IIIB
The
disease
MPS
IIIB,
also
known
as
Sanfilippo
syndrome
type
IIIB,
is
an
inherited
disease.
It
is
one
of
a
group
of
eleven
different
genetic
diseases
known
as
the
MPS
disorders.
The
MPS
disorders
are
all
classified
as
lysosomal
storage
diseases.
Other
better-known
lysosomal
storage
diseases
that
occur
in
humans
include
Tay-Sachs
disease
and
Gaucher
disease.
The
feature
that
unites
lysosomal
storage
diseases
is
that
they
have
abnormal
lysosomal
function.
The
lysosome
is
an
important
structure
of
virtually
all
cells
in
the
body,
and
serves
as
the
"garbage
disposal"
of
the
cell.
In
humans
MPS
IIIB
is
seen
in
approximately
one
out
of
73,000
live
births.
The
lysosome
is
essentially
a
"bag"
within
cells
of
the
body,
which
is
filled
with
special
enzymes.
The
lysosome's
function
is
to
disassemble
large
molecules
of
a
cell
that
need
to
be
recycled
or
disposed
of.
The
way
in
which
molecules
are
dissembled
in
the
lysosomes
involves
a
series
of
steps,
something
like
an
automobile
assembly
line,
but
in
reverse.
In
place
of
the
"disassembly"
line
workers
who
each
do
one
specific
job,
the
lysosome
employs
many
different
enzymes,
which
again
have
just
one
job
each.
These
enzymes,
when
all
are
present,
disassemble
molecules
in
an
orderly
and
efficient
manner.
When
one
of
the
enzymes
is
missing,
due
to
mutations
in
all
copies
of
the
gene
for
that
specific
enzyme,
the
orderly
processes
of
disassembly
stops,
and
large
undegraded
molecules
begin
to
accumulate
in
the
lysosomes,
hence
the
name
lysosomal
storage
disease.
Eventually
the
lysosomes
of
a
cell
become
so
large,
that
it
interferes
with
the
normal
job
of
a
cell,
and
the
cells
become
sick
or
die,
which
leads
to
the
clinical
signs
and
symptoms
of
the
disease.
In
MPS
IIIB
the
compound
which
is
stored
is
called
heparan
sulfate.
Heparan
sulfate
is
one
of
a
number
of
compounds
known
as
glycosaminoglycans
(GAGs),
which
are
themselves
long
strings
of
chemically
modified
sugar
molecules
important
in
structures
like
bone
and
cartilage
and
in
the
communication
machinery
betweens
cells
in
the
body,
especially
in
the
brain.
The
term
mucopolysaccharide
is
actually
on
old-fashioned
term
for
GAG,
hence
the
name
mucolpolysaccharidosis.
The
enzyme
that
is
not
functioning
appropriately
in
MPS
IIIB
is
called
N-acetyl-a-D-glucoseaminidase
(NAGLU).
What
are
the
symptoms
of
MPS
IIIB
In
humans
the
signs
and
symptoms
of
MPS
IIIB
are
related
to
the
mental
deterioration
that
is
seen.
By
the
age
of
3-6
years,
affected
children
start
to
show
delayed
development.
The
mental
deterioration
progresses
through
mental
retardation
and
finally
to
dementia.
As
part
of
this
progression
the
children
may
show
behaviorial
abnormalities
which
can
include
hyperactivity,
poor
sleeping
patterns,
and
aggressive
and
destructive
behaviors.
If
the
children
have
acquired
speech
and
toilet
training
skills
these
are
eventually
lost.
In
the
last
stages
of
the
disease
the
children
lose
the
ability
to
walk
or
feed
themselves.
Most
do
not
see
their
third
decade
of
life.
At
this
time
there
is
no
proven
and
effective
treatment
for
this
disease.
To
learn
more
about
this
condition
in
children
one
can
visit
www.mpssociety.org
The
clinical
signs
in
the
dogs
are
in
many
ways
similar
to
the
children,
in
that
the
clinical
signs
are
related
to
the
brain
disease.
However,
the
dogs
differ
from
children
in
two
important
ways.
The
age
of
onset
is
seen
in
the
dogs
during
early
adulthood,
and
the
clinical
signs
are
related
to
a
particular
part
of
the
brain
called
the
cerebellum.
The
cerebellum
plays
an
important
role
in
balance
and
smooth
and
coordinated
movement.
The
clinical
signs
in
the
dogs
have
been
reported
to
appear
between
2-4
years
of
age,
and
include
tremor,
difficulty
balancing,
walking,
negotiating
obstacles
such
as
stairs,
head
tilts,
falling
to
both
directions,
and
other
clinical
signs
associated
with
the
generalized
balance
problems
.
Some
have
reported
a
change
in
coat
color
from
black
to
auburn,
however,
coat
changes
can
be
associated
with
many
other
diseases
and
illnesses.
In
the
dogs
the
disease
is
progressive,
and
the
initial
problems
with
balance
become
worse
until
the
dogs
cannot
stand,
walk,
eat,
etc.,
without
a
great
deal
of
difficulty.
Owners
have
eventually
chosen
to
have
their
dogs
euthanized.
This
was
usually
chosen
within
1-2
years
after
clinical
signs
were
first
recognized.
Affected
bitches
are
fertile,
and
can
have
pups.
We
expect
that
affected
males
may
also
be
fertile,
but
we
have
not
observed
this.
How
is
MPS
IIIB
inherited?
The
inheritance
pattern
of
MPS
IIIB
is
autosomal
recessive.
As
is
the
case
with
all
autosomal
genes
(genes
not
found
on
the
sex-chromosomes),
an
individual
has
two
copies
of
a
specific
gene,
one
copy
on
each
of
a
pair
of
autosomes.
With
MPS
IIIB,
if
an
individual
is
affected
with
the
disease,
both
of
the
NAGLU
genes
that
the
affected
dog
inherited
were
the
mutant
form
of
the
gene.
Both
males
and
females
are
equally
capable
of
having
the
disease,
in
other
words
the
disease
in
not
sex-linked,
and
inheritance
of
the
mutant
copy
of
the
gene
must
come
from
both
the
sire
and
dam.
Carriers,
or
individuals
that
have
inherited
one
normal
copy
and
one
mutant
copy
the
NAGLU
gene
are
absolutely
normal,
and
will
not
have
signs
of
the
disease.
Parents
of
an
affected
animal
are
what
is
called
"obligate
carriers",
in
other
words,
since
an
affected
was
produced
from
them,
they
must
both
be
carriers
of
a
mutant
copy
of
the
NAGLU
gene.
Is
there
a
DNA
test
and
if
so
what
do
the
DNA
test
results
mean?
There
is
now
a
DNA
test
available.
We
have
found
a
mutation
in
the
NAGLU
gene
in
the
Schipperke
breed
and
the
test
for
this
mutation
is
offered
through
the
Josephine
Deubler
Genetic
Disease
Testing
Laboratory
at
the
School
of
Veterinary
Medicine
at
the
University
of
Pennsylvania.
The
DNA
diagnosis
will
report
a
result
as
either
affected
(affected
with
the
disease-both
genes
are
mutant),
carrier
(clinically
normal-one
mutant
and
one
normal
gene),
or
normal
(clinically
normal-both
genes
normal).
This
test
is
the
most
efficient
way
to
diagnose
affected
animals
with
MPS
IIIB.
It
is
also
the
only
way
to
be
sure
of
whether
a
breeding
animal
is
a
carrier
or
a
normal
dog.
This
DNA
test
can
be
run
from
DNA
extracted
from
either
EDTA
blood
(lavender
top
tube)
or
from
special
cytology
brushes
used
to
get
a
sample
of
cells
form
the
inside
of
the
mouth
(cheek
swabs).
Please
see
the
attached
documents
for
instructions
on
the
collections
and
submission
of
samples.
How
do
I
go
about
getting
my
dog
tested?
For testing information please visit PennGen website http://research.vet.upenn.edu/penngen and contact them if you have any questions.
Who
receives
notification
of
the
DNA
test
results?
It
is
the
policy
of
the
Josephine
Duebler
Genetic
Disease
Testing
Laboratory
that
all
results
are
kept
completely
confidential.
No
results
are
released
to
anyone
other
than
the
individual
that
submitted
the
sample.
This
may
be
the
veterinarian,
the
owner,
or
an
agent
for
the
owner.
No
result
that
is
identified
as
being
from
a
specific
dog
is
made
in
scientific
communications
or
publications
unless
by
the
written
consent
of
the
owner.
Results
will
be
sent
out
within
3-4
weeks
from
the
receipt
of
samples.
How
common
is
this
disease
and
how
long
has
it
been
in
the
Schipperke
breed?
We
cannot
be
certain
of
how
common
this
disease
is
in
the
Schipperke,
either
in
terms
of
how
many
affecteds
there
are
or
how
many
carriers
there
are.
We
had
initially
seen
two
cases
of
this
disease,
which
we
diagnosed
from
samples
submitted
for
analysis
to
the
school's
metabolic
genetic
screening
laboratory.
Since
then
we
have
documented
MPS
IIIB
affected
dogs
in
a
total
of
five
different
families.
From
comparisons
of
the
pedigrees
of
these
dogs
we
can
say
that
the
nearest
and
most
likely
common
ancestor
was
an
animal
found
as
far
back
as
eleven
generations
in
some
pedigrees.
This
would
mean
that
the
mutant
gene
may
be
very
broadly
distributed
in
the
Schipperke
population.
We
cannot
predict
what
sort
of
frequency
of
carriers
there
may
be
in
the
population
at
large
without
a
controlled
study.
However
a
similar
lysosomal
storage
disease,
called
ß-mannosidosis,
which
was
seen
in
the
Salers
breed
of
cattle
was
shown
to
have
a
carrier
frequency
of
15%.
If
a
similar
carrier
frequency
was
to
be
seen
in
the
Schipperke
breed
this
would
mean
that
on
average,
up
to
one
out
of
every
seven
dogs
could
be
a
carrier.
If
the
mutation
is
so
old,
why
has
this
not
been
seen
before?
Although
it
is
impossible
to
prove,
we
feel
that
this
disease
has
been
seen
before,
but
was
just
not
recognized.
There
is
a
report
in
the
scientific
literature
that
describes
a
case
of
a
lysosomal
storage
disease
in
a
Schipperke
that
was
published
in
1993.
The
authors
were
unable
to
say
exactly
which
lysosomal
storage
disease
it
was.
Their
findings
however
were
nearly
identical
to
what
we
have
seen
in
two
cases
from
the
late
1990s.
Many
factors
may
have
contributed
to
MPS
IIIB
not
having
been
recognized
earlier.
It
may
be
that
the
mutant
gene
is
rare
enough
in
the
population
at
large,
that
the
chances
of
two
carriers
being
mated
and
producing
offspring
was
low,
and
such
sporadic
cases
escaped
the
attention
of
veterinarians,
breeders,
and
owners.
The
clinical
signs
of
MPS
IIIB
are
not
themselves
specific
to
MPS
IIIB,
but
can
be
caused
by
a
host
of
other
illnesses.
The
disease
is
seen
in
adulthood,
which
is
not
usually
the
case
with
such
severe
genetic
diseases.
Many
owners
may
have
declined
a
post-mortem
examination.
Unless
a
post-mortem
examination
was
conducted,
it
is
unlikely
that
anyone
who
had
a
case
of
this
disease
would
have
known
about
it.
Even
if
a
post-mortem
examination
was
conducted
all
that
could
be
determined
was
that
the
patient
had
a
lysosomal
storage
disease.
Knowledge
of
these
sorts
of
diseases
is
limited
among
medical
professionals.
Very
few
veterinarians
will
have
ever
heard
of
this
disease,
and
if
so,
never
in
a
dog,
since
the
Schipperke
breed
is
the
first
case
of
the
diagnosis
of
MPS
IIIB
in
any
dog.
The
difficult
in
finding
an
accurate
diagnosis
is
not
a
situation
that
is
unique
to
veterinary
medicine,
as
families
whose
children
have
this
disease
are
not
infrequently
given
other
diagnoses
before
a
definitive
diagnosis
of
MPS
IIIB
is
made.
We
believe
a
combination
of
all
these
factors
may
have
served
to
obscure
earlier
cases
of
this
disease.
Who
should
have
their
animals
tested?
Considering
the
fact
that
the
disease
is
progressive,
cannot
be
treated,
is
fatal,
and
devastating
to
the
dogs
and
their
families,
we
would
recommend
that
every
breeding
animal
be
DNA
tested
for
this
disease.
Additionally,
all
pups
that
are
waiting
to
be
placed
in
permanent
homes
should
be
considered
for
testing,
to
spare
their
new
owners
a
great
deal
of
anguish
and
anxiety.
Any
non-breeding
animal
that
is
under
three
years
of
age
may
be
a
candidate
for
testing
to
identify
if
it
is
affected
and
will
develop
clinical
signs.
However
it
must
be
mentioned
that
there
is
no
treatment
for
this
disease,
hence
testing
of
such
animals
is
probably
useful
only
to
relieve
the
anxiety
of
owners
who
know
that
their
pet
is
at
risk,
i.e.
an
animal
whose
parents
are
known
to
be
carriers.
What
do
I
do
if
I
have
pups
waiting
to
go
to
homes?
Another
consequence
of
offering
a
new
DNA
test
is
that
there
may
be
cases
where
breedings
are
in
progress
or
where
pups
are
on
the
ground,
and
parents
have
either
not
been
tested,
or
perhaps
are
known
to
be
carriers.
In
a
situation
such
as
this
where
the
breeder
has
a
concern
about
placing
an
affected
pup,
we
will
make
a
priority
of
testing
parents
of
such
pups.
Please
submit
these
parental
samples
together,
with
sire
and
dam
of
litter
in
the
same
submission.
If
both
parents
are
found
to
be
or
known
to
be
carriers,
pups
that
are
waiting
or
due
to
be
placed
in
homes
will
also
be
tested
on
a
priority
basis.
By
pups
waiting
to
go
to
homes
we
mean
young
pups
going
to
their
first
home
from
the
breeder.
On
the
submission
form
there
is
a
place
to
note
the
reason
for
screening,
there
is
a
box
marked
"other".
Check
that
box,
and
write
"puppy
waiting
for
placement"
or
"sire
and
dam
of
litter
waiting
to
be
placed".
Please
do
not
abuse
this
privilege.
The
turn
around
on
such
samples
is
not
rush,
but
will
be
the
normal
3-4
week
turn
around.
This
provision
will
be
in
effect
for
any
breeding
conducted
before
April
1,
2003.
What
do
I
do
if
I
am
planning
a
breeding?
As
we
anticipate
much
of
our
initial
testing
is
to
be
done
on
breeding
animals,
we
feel
it
impractical
to
offer
a
priority
testing
because
a
breeding
is
eminent.
In
cases
were
a
breeding
is
eminent,
we
must
regretfully
recommend
that
the
planned
breeding
take
place
after
a
diagnosis
is
provided.
We
regret
the
delay
this
may
cause,
but
in
a
worse
case
scenario,
it
will
only
delay
breeding
by
one
heat
cycle
of
a
bitch.
What
should
I
do
if
I
have
an
affected
dog?
Unfortunately
there
is
no
treatment
for
this
disease.
Once
an
animal
has
begun
to
show
clinical
signs,
all
that
can
be
done
is
to
provide
a
safe
environment,
such
as
one
without
stairs,
or
obstacles,
which
might
lead
to
falls
or
make
getting
around
difficult.
The
decision
of
when
to
elect
euthanasia
for
a
sick
pet
is
a
difficult
one,
and
must
be
made
by
balancing
the
importance
of
the
bond
between
the
owner
and
their
pet,
and
the
quality
of
life
of
their
pet.
Under
no
circumstances
can
we
recommend
that
non-symptomatic
animals
be
euthanized.
Although
the
lifespan
of
dogs
with
this
disease
is
much
shorter
than
normal,
until
they
become
clinically
affected,
they
are
absolutely
normal,
and
depending
on
the
clinical
course
of
the
disease
in
the
individual,
they
can
have
many
months
of
quality
life
after
clinical
signs
appear.
The
difference
between
owning
an
affected
versus
and
unaffected
dog,
is
that
the
owner
has
a
very
good
idea
of
when
and
why
they
may
face
the
decision
to
elect
euthanasia
for
their
pet.
If
you
are
a
breeder
and
find
that
you
have
an
unplaced
affected
pup,
or
if
you
are
an
owner
of
an
affected
dog,
and
you
would
like
to
know
how
you
can
help
to
further
our
efforts
to
find
a
treatment
and
a
cure
for
this
devastating
disease,
we
encourage
you
to
contact
Penn Gen at http://research.vet.upenn.edu/penngen or at e-mail address penngen@vet.upenn.edu
Questions:
Please
submit
any
questions
you
may
have
regarding
MPS
IIIB
in
Schipperkes
to
the
SCA's
Heath
and
Genetics
Chair.
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Send correspondence to:
Sue Geiger
Central Rockies Schipperke Club
of Greater Denver
3228 S. Garrison St. Apt.299
Lakewood, Colorado 80227
Email: CRSCSecretary@yahoo.com
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