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Pyruvate dehydrogenase deficiency and epilepsy.
[pyruvate dehydrogenase deficiency]
The
pyruvate
dehydrogenase
complex
(
PDHc
)
is
a
mitochondrial
matrix
multienzyme
complex
that
provides
the
link
between
glycolysis
and
the
tricarboxylic
acid
(
TCA
)
cycle
by
catalyzing
the
conversion
of
pyruvate
into
acetyl-
CoA
.
PDHc
deficiency
is
one
of
the
commoner
metabolic
disorders
of
lactic
acidosis
presenting
with
neurological
phenotypes
that
vary
with
age
and
gender
.
In
this
mini-review
,
we
postulate
mechanisms
of
epilepsy
in
the
setting
of
PDHc
deficiency
using
two
illustrative
cases
(
one
with
pyruvate
dehydrogenase
complex
E
1
-
alpha
polypeptide
(
PDHA
1
)
deficiency
and
the
second
one
with
pyruvate
dehydrogenase
complex
E
1
-
beta
subunit
(
PDHB
)
deficiency
(
a
rare
subtype
of
PDHc
deficiency
)
)
and
a
selected
review
of
published
case
series
.
PDHc
plays
a
critical
role
in
the
pathway
of
carbohydrate
metabolism
and
energy
production
.
In
severe
deficiency
states
the
resulting
energy
deficit
impacts
on
brain
development
in
utero
resulting
in
structural
brain
anomalies
and
epilepsy
.
Milder
deficiency
states
present
with
variable
manifestations
that
include
cognitive
delay
,
ataxia
,
and
seizures
.
Epileptogenesis
in
PDHc
deficiency
is
linked
to
energy
failure
,
development
of
structural
brain
anomalies
and
abnormal
neurotransmitter
metabolism
.
The
use
of
the
ketogenic
diet
bypasses
the
metabolic
block
,
by
providing
a
direct
source
of
acetyl-
CoA
,
leading
to
amelioration
of
some
symptoms
.
Genetic
counseling
is
essential
as
PDHA
1
deficiency
(
commonest
defect
)
is
X-
linked
although
females
can
be
affected
due
to
unfavorable
lyonization
,
while
PDHB
and
PDH
phosphatase
(
PDP
)
deficiencies
(
much
rarer
defects
)
are
of
autosomal
recessive
inheritance
.
Research
is
in
progress
for
looking
into
animal
models
to
better
understand
pathogenesis
and
management
of
this
challenging
disorder
.
