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A novel CaSR mutation presenting as a severe case of neonatal familial hypocalciuric hypercalcemia.
[familial hypocalciuric hypercalcemia]
Familial
Hypocalciuric
Hypercalcemia
(
FHH
)
is
a
generally
benign
disorder
caused
by
heterozygous
inactivating
mutations
in
the
Calcium
-
Sensing
Receptor
(
CaSR
)
gene
resulting
in
altered
calcium
metabolism
.
We
report
a
case
of
unusually
severe
neonatal
FHH
due
to
a
novel
CaSR
gene
mutation
that
presented
with
perinatal
fractures
and
moderate
hypercalcemia
.
CASE
OVERVIEW
:
A
female
infant
was
admitted
at
2
 
weeks
of
age
for
suspected
non-accidental
trauma
(
NAT
)
.
Laboratory
testing
revealed
hypercalcemia
(
3
.
08
 
mmol
/
L
)
,
elevated
iPTH
(
20
.
4
pmol
/
L
)
and
low
urinary
calcium
clearance
(
0
.
0004
)
.
Radiographs
demonstrated
multiple
healing
metaphyseal
and
rib
fractures
and
bilateral
femoral
bowing
.
The
femoral
deformity
and
stage
of
healing
were
consistent
with
prenatal
injuries
rather
than
non-accidental
trauma
(
NAT
)
.
Treatment
was
initiated
with
cholecalciferol
,
400
 
IU
/
day
,
and
by
6
 
weeks
of
age
,
iPTH
levels
had
decreased
into
the
high
-normal
range
.
Follow
up
radiographs
demonstrated
marked
improvement
of
bone
lesions
by
3
 
months
.
A
CaSR
gene
mutation
study
showed
heterozygosity
for
a
T
>
C
nucleotide
substitution
at
c
.
1664
in
exon
6
,
resulting
in
amino
acid
change
I
555
T
in
the
extracellular
domain
consistent
with
a
missense
mutation
.
Her
mother
does
not
carry
the
mutation
and
the
father
is
unknown
.
At
18
 
months
of
age
,
the
child
continues
to
have
relative
hyperparathyroidism
and
moderate
hypercalcemia
but
is
otherwise
normal
.
This
neonate
with
intrauterine
fractures
and
demineralization
,
moderate
hypercalcemia
and
hyperparathyroidism
was
found
to
have
a
novel
inactivating
missense
mutation
of
the
CaSR
not
detected
in
her
mother
.
Resolution
of
bone
lesions
and
reduction
of
hyperparathyroidism
was
likely
attributable
to
the
natural
evolution
of
the
disorder
in
infancy
as
well
as
the
mitigating
effect
of
cholecalciferol
treatment
.
Diseases
Validation
Diseases presenting
"rib fractures and bilateral femoral bowing"
symptom
familial hypocalciuric hypercalcemia
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