1. What
is
Lowe
Syndrome
and
what
are
the
causes
Lowe
syndrome
is
a
rare
heritable
defect
with
the
major
symptoms
in
eye,
kidney
and
central
nervous
system
due
to
dysfunc:on
of
regulatory
OCRL1.
Pa:ents
with
renal
diseases
worsen
with
increased
age
while
younger
pa:ents
are
also
diagnosed
with
renal
fanconi
syndrome
where
substances
are
lost
in
body.
Current
treatment
includes
medica:ons
to
replace
the
lost
substances
and
several
ways
to
detect
the
defects.
However,
more
studies
need
to
be
done
to
understand
deeper
mechanism
underlying
Lowe
syndrome.
Prensted
by:
Medeha
Nahiyan,
Hsin-­‐Yu
Chen,
Wing
Tung
Wong
Lowe
Syndrome
was
first
discovered
in
1952
by
Lowe
and
colleagues.
It
is
a
gene:c
X-­‐linked
disease
so
female
tend
to
be
carriers
while
the
disease
primarily
affects
males.
Rare
condi:on
with
prevalence
of
1
in
500,000
people
is
diagnosed
with
Lowe
syndrome.
It
is
caused
by
the
defec:ve
muta:on
in
the
OCRL
gene
and
affects
eyes,
kidney
and
nervous
system.
Therefore
it
is
also
known
as
Oculo-­‐Cerebro
Renal
Syndrome.
In
this
defect,
protein
phosphatase
plays
a
significant
role
on
cellular
processes
like
enzyme
ac:vity
and
signalling
pathway.
The
muta:on
will
cause
serious
problem
in
body
func:on.
• OCRL
gene
• Protein
OCRL1-­‐
one
of
5-­‐phosphatase
group
• Located
in
the
trans-­‐golgi
network
• Involved
in
ac:n
polymerisa:on
• Muta:on
of
OCRL
mis-­‐folding
and
malfunc:on
of
the
protein
mul:system
disorders
• Cataracts
presented
in
all
pa:ents
from
birth
-
Opaque
deposit
in
the
lens
of
the
eye
-
Seen
in
place
of
the
black
pupil
of
the
eye
-
Develops
in
utero
due
to
the
migra:on
of
crystalline
embryonic
epithelium
-
Both
eyes
are
affected
• Glaucoma
- condi:on
due
to
the
build-­‐up
of
pressure
within
the
eye
• Bicarbonate,
salts
such
as
potassium,
sodium
and
water
appear
in
urine
in
early
symptoms
at
younger
ages
- known
as
renal
fanconi
syndrome
- other
symptoms
including
aminoaciduria,
hypokalemia,
hypercalciuria,
was:ng
of
renal
phosphate
and
proximal
renal
tubular
acidosis
• Renal
disease
worsens
with
an
increase
of
age
• Chronic
renal
failure
at
older
ages
• Cogni:ve
and
behavioural
impairments
- self-­‐
abusive,
non-­‐coopera:ve
and
violent
- Mental
retarda:on,
Hypotonia,
Seizures
and
febrile
convulsion
• Difficult
• Family
history
- DNA
analysis
- Enzyme
difficiency
analysis
Ø Phospha:dylinositol-­‐4,5-­‐bisphosphate
difficiency
- Female
carrier-­‐
ophthalmologist
Ø Punctuate
opaci:es
in
len:cular
cortex
• Technique
- MRI
Ventriculomegaly,
mul:ple
periventricular
cys:c
lesion
- Neuroimaging
delayed
myelina:on,
dilated
perivascular
spaces,
etc.
• No
cure
• Glaucoma
(Eye)
- Glasses
and
contact
lenses-­‐improve
vision
- Eye
drops-­‐
relieve
pressure
- (early)
surgery-­‐remove
corneal
keloids
• Hypotonia
(Nervous
system)
- Tube
feeding
• Proximal
tubular
dysfunc:on
- NaHCO3,
KHCO3
or
citrate
Figure2.
Organs
affected
in
Lowe
syndrome
(retrieved
from
Mehta,Z,
et
al,
2014).
-­‐Charnas
LR,
Bernardini
I,
Rader
D,
Hoeg
JM,
Gahl
WA
Clinical
and
laboratory
findings
in
the
oculocerebrorenal
syndrome
of
Lowe,
with
special
reference
to
growth
and
renal
func:on.
-­‐Choudhury
R,
Diao
A,
Zhang
F,
Eisenberg
E,
Saint-­‐Pol
A,
Williams
C,
-­‐
Konstantakopoulos
A,
Lucocq
J,
Johannes
L,
Rabouille
C,Greene
L,
Lowe
M.
Lowe
Syndrome
protein
OCRL1
interacts
with
clathrin
and
regulates
protein
trafficking
between
endosomes
and
the
trans-­‐Golgi
network.
Mol
Biol
Cell
(in
press).
-­‐Demmer
LA,
Wippold
FJ
2nd,
Dowton
S.
Periventricular
white
maeer
cys:c
lesions
in
Lowe
(oculocerebrorenal)
syndrome.
A
new
MR
finding.
Pediatr
Radiol.
1992;
22(1):76-­‐7.
-­‐Faucherre
A,
Desbois
P,
Nagano
F,
satre
V,
Lunardi
J,
Gacon
G,
Dorseuil
O,
Lowe
Syndrome
protein
OCRL1
is
translocated
to
membrane
ruffles
upon
Rac
GTPase
ac:va:on:
a
new
perspec:ve
on
Lowe
Syndrome
pathophysiology,
Jun
1,
2005,
PubMed.
-­‐Janne
PA,
Suchy
SF,
Bernard
D,
MacDonald
M,
Crawley
J,
Grinberg
A,
Wynshaw-­‐
Boris
A,
Westphal
H,
Nussbaum
RL,
Func:onal
overlap
between
murine
Inpp5b
and
ocrl1
may
explain
why
deficiency
of
the
murine
ortholog
for
ORCL1
does
not
cause
Lowe
syndrome
in
mice,
May
15,1998,
PubMed.
-­‐Lowe
M,
Structure
and
func:on
of
the
Lowe
Syndrome
protein
OCRL1,
Sep
5,
2005,
PubMed.
-­‐Mario
Loi,
Lowe
Syndrome,
May
18,
2006,
PubMed.
Figure1.
Site
where
cataracts
form
(retrieved
from
www.holteyecare.com%2Fcataracts.html&h=nAQEQn1hX