Rare Diseases Symptoms Automatic Extraction
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Clinical and molecular heterogeneity in patients with the cblD inborn error of cobalamin metabolism.
[homocystinuria without methylmalonic aciduria]
To
describe
3
patients
with
the
cblD
disorder
,
a
rare
inborn
error
of
cobalamin
metabolism
caused
by
mutations
in
the
MMADHC
gene
that
can
result
in
isolated
homocystinuria
,
isolated
methylmalonic
aciduria
,
or
combined
homocystinuria
and
methylmalonic
aciduria
.
Patient
clinical
records
were
reviewed
.
Biochemical
and
somatic
cell
genetic
studies
were
performed
on
cultured
fibroblasts
.
Sequence
analysis
of
the
MMADHC
gene
was
performed
on
patient
DNA
.
Patient
1
presented
with
isolated
methylmalonic
aciduria
,
patient
3
with
isolated
homocystinuria
,
and
patient
2
with
combined
methylmalonic
aciduria
and
homocystinuria
.
Studies
of
cultured
fibroblasts
confirmed
decreased
synthesis
of
adenosylcobalamin
in
patient
1
,
decreased
synthesis
of
methylcobalamin
in
patient
3
,
and
decreased
synthesis
of
both
cobalamin
derivatives
in
patient
2
.
The
diagnosis
of
cblD
was
established
in
each
patient
by
complementation
analysis
.
Mutations
in
the
MMADHC
gene
were
identified
in
all
patients
.
The
results
emphasize
the
heterogeneous
clinical
,
cellular
and
molecular
phenotype
of
the
cblD
disorder
.
The
results
of
molecular
analysis
of
the
MMADHC
gene
are
consistent
with
the
hypothesis
that
mutations
affecting
the
N
terminus
of
the
MMADHC
protein
are
associated
with
methylmalonic
aciduria
,
and
mutations
affecting
the
C
terminus
are
associated
with
homocystinuria
.