00:01
In this presentation,
we're going to talk about
Inborn Errors of Metabolism.
00:06
And this is just going to be an
overview because there are many.
00:10
So what are
Inborn Errors of Metabolism.
00:14
This is a congenital condition,
and it's the absence or
abnormality of an enzyme,
or that enzymes cofactor.
00:24
So what does that
mean for our patient?
We have many substances
in our bodies,
and many that we take in
like protein, for example.
00:34
And you need enzymes
or the cofactor of those enzymes
to break those substances down
so that our body can use them.
00:43
When these substances are
not able to be broken down,
because there's a deficiency
of an enzyme or the cofactor,
what happens is we get an
accumulation of metabolites
or an accumulation of those
substances in the body.
00:58
And that can have really
extreme consequences.
01:03
Now, sometimes, if the enzyme
is missing or abnormal,
we'll actually have a
deficiency of the metabolites.
01:10
We don't have the
substances in the body
that we need for our metabolism
and for general functioning.
01:18
So what causes an
inborn error of metabolism?
These are mostly
autosomal recessive.
01:25
So this means if you remember
from your genetics,
that the offspring is going
to inherit two copies of the gene,
one from each parent.
01:33
And the genes usually come
from non sex chromosomes.
01:36
And those copies must both have
the condition that's
going to cause the inborn error.
01:44
So there are many types of
inborn errors of metabolism.
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And I want to stress that you do not
need to know each inborn error.
01:54
There's some broad categories
of these inborn errors.
01:57
You'll see organic acidemia
or amino acid disorders.
02:03
And these cause specific diseases.
These also have categories.
02:08
So you might have a
lysosomal storage disease.
02:12
A disease like phenylketonuria,
where you have too many
ketones in your body.
02:18
There's peroxisomal disorders,
mitochondrial diseases,
where your mitochondria
just are not working correctly.
02:28
Glycogen storage diseases.
02:31
And we know if you have
trouble storing glycogen
that you're going to have trouble
with your metabolism.
02:37
Urea cycle disorders.
02:40
So there are many different types.
02:43
So, inborn errors of metabolism
can either be a
single enzyme deficiency
and that's the most
common thing that happens
or you might have abnormalities
in more than one enzyme.
02:54
And when you have
abnormalities in more than one,
you're usually going to affect
several metabolic steps.
03:02
So what does this mean
for our patients?
When you have a single
enzyme deficiency,
which is the most common,
you might have an
accumulation of metabolites.
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An example of this would
be Alkaptonuria.
03:16
And this results in an
accumulation of homogentisic acid.
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You might have a
deficiency of metabolites
as what happens
in the MCAD disease,
and that is going to result
in an inability for the body
to make keto acids.
03:35
Additionally,
if you have abnormalities
in more than one enzyme,
as in the case of vitamin B 12
transport and synthesis,
you might have an accumulation of
methylmalonic acid and homocysteine.
03:49
So this affects multiple steps
in the metabolism.
03:53
So how often does this happen?
It turns out that the
individual inborn error rates
is actually pretty rare.
04:00
It's low,
it's less than 100,000 live births.
04:04
But when you combine this
with the fact that
there are many, many different types
of inborn errors of metabolism,
it actually becomes
a little more common.
04:13
So one in 800 to 2500 live births,
depending on where you are,
may have an inborn
error of metabolism.
04:24
So what are patients going to look
like if they have inborn errors?
Well, when your
metabolism is affected,
it's going to include findings
in almost every body system.
04:35
Primarily what we're going
to notice first
our problems with
the neurologic system
and with the
gastrointestinal system.
04:43
So you might see things and
especially chronic symptoms like
failure to thrive and growth delay.
04:50
Maybe these patients aren't getting
their developmental milestones.
04:53
They have a developmental delay,
or they might even lose
developmental milestones.
04:59
Infants that were able to
sit up and smile at you
now no longer have the
ability to sit on their own.
05:05
So that's what is meant by
regression of milestones.
05:09
They might experience
cardiomyopathy,
they might have hepatomegaly.
05:13
So their liver is really big.
05:14
You can feel it way down
below their ribs.
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They might have spastic diplegia,
meaning that they have
difficulty walking.
05:23
More acute symptoms are going to be
symptoms that are
consistent with shock.
05:28
So you might have dehydration.
05:30
They might be hypoglycemic,
making them shaky.
05:33
They might be in a
prolonged fasting state,
because they just
haven't been able to eat
because they're nauseous,
and they're vomiting.
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And they are under
extreme amounts of stress.
05:46
So that can progress
into a metabolic emergency.
05:51
If your patient is
continually vomiting,
they're becoming lethargic.
Maybe even falling into a coma.
05:58
Experiencing seizures,
or rapid deep breathing.
06:02
That is all metabolic emergency.
06:05
Additionally, they might be
breaking down their own muscles,
which is rhabdomyolysis.
06:10
Might be experiencing hypothermia.
06:13
Hypothermia is often associated
with more minor illness
and then hyperthermia or high
temperatures might follow that.
06:22
If you have a patient that
has any of these symptoms
that can't be explained
by an illness or other condition,
we have to consider the possibility
of an inborn error of metabolism.
06:35
Inborn errors can really occur
in any age group.
06:38
But the most severe forms
are usually going to be found
as a neonate.