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Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives.
[zellweger syndrome]
The
peroxisome
biogenesis
disorders
(
PBD
)
are
a
heterogeneous
group
of
autosomal
recessive
disorders
in
which
peroxisome
assembly
is
impaired
,
leading
to
multiple
peroxisome
enzyme
deficiencies
,
complex
developmental
sequelae
and
progressive
disabilities
.
Mammalian
peroxisome
assembly
involves
the
protein
products
of
16
PEX
genes
;
defects
in
14
of
these
have
been
shown
to
cause
PBD
.
Three
broad
phenotypic
groups
are
described
on
a
spectrum
of
severity
:
Zellweger
syndrome
is
the
most
severe
,
neonatal
adrenoleukodystrophy
is
intermediate
and
infantile
Refsum
disease
is
less
severe
.
Another
group
is
Rhizomelic
chondrodysplasia
punctata
spectrum
.
Recently
,
atypical
phenotypes
have
been
described
,
indicating
that
the
full
spectrum
of
these
disorders
remains
to
be
identified
.
For
most
patients
,
there
is
a
correlation
between
clinical
severity
and
effect
of
the
mutation
on
PEX
protein
function
.
Diagnosis
relies
on
biochemical
measurements
of
peroxisome
functions
and
PEX
gene
sequencing
.
There
are
no
targeted
therapies
,
although
management
protocols
have
been
suggested
and
research
endeavors
continue
.
In
this
review
we
will
discuss
peroxisome
biology
and
PBD
,
and
research
contributions
to
pathophysiology
and
treatment
.
Diseases
Validation
Diseases presenting
"complex developmental sequelae and progressive disabilities"
symptom
neonatal adrenoleukodystrophy
zellweger syndrome
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