00:01
Let's start with disorders of carbohydrate metabolism.
00:05
We can see patients with problems in glucose metabolism,
fructose metabolism, and galactose metabolism.
00:14
I've drawn here the galactose differently than glucose
because the OH group goes off in a different direction.
00:20
It's a cartoon but I think it's effective.
00:23
Glycogen storage diseases
are probably the most common issue around glucose metabolism.
00:29
Essentially, enzyme defects in glycogen breakdown
result in an inability to make glucose
after a short period of fasting in the liver and the muscle.
00:42
So patients can present with both hepatic disease and muscle disease.
00:46
In other words, they're having a problem getting the glucose
out of their glycogen stores.
00:52
With hepatic disease, a short fast can cause hypoglycemia.
00:58
It usually shows up in the first 6 months of life
as children start to space out their feeds.
01:05
Typically, a newborn baby is eating every 2 hours,
the glycogen storage aren't that important.
01:10
As they get older, they rely on their glycogen storage more
because they're going longer distances between feeds.
01:17
These patients can present with muscle weakness
and they can present with hepatic cirrhosis at times.
01:24
The muscle disease is a progressive muscle weakness
and sometimes can involve the heart as well.
01:31
And in some varieties of glycogen storage diseases,
the cardiomyopathy is the most important thing.
01:38
Any child with cardiomyopathy is primarily gonna present with fatigue.
01:42
Let's go through three really common glycogen storage diseases.
01:48
The first one is Von Gierke's disease.
01:51
And I like to think about Von Gierke's as primarily in the liver.
01:56
This is also glycogen storage disease type 1.
01:59
These patients will present with a profoundly challenging hypoglycemia.
02:04
They will have hepatomegaly from their liver involvement.
02:07
They will develop hyperlipidemia as well.
02:10
Because of their underlying problem,
they may have growth failure but they will not primarily have weakness.
02:17
Most of their diseases related to the liver.
02:20
That's as opposed to Pompe's disease.
02:24
Pompe's disease can be very severe in childhood
or it can develop later.
02:30
But this is glycogen storage disease type 2
and it's primarily involving the heart.
02:36
They do not develop hypoglycemia.
02:39
They still do get some hepatomegaly
but it can either be very severe with a inevitable death
by the age of 2 or can be more benign.
02:51
Clearly, a heart failure is the most important heralding symptom
of Pompe's disease.
02:56
The last example would be McArdle's
and when I think of McArdle's I think of muscle.
03:02
Muscle McArdle's.
03:03
This is glycogen storage disease type 5.
03:07
It really only has muscle involvement,
so these patients develop the weakness
but not as much of the other symptoms.
03:15
They may develop renal problems from myoglobin breakdown
and sledging in the kidney causing renal damage,
so monitoring for that is important.
03:25
Let's switch to another type of sugar which is galactosemia.
03:31
Remember that galactose is metabolized through a pathway
involving two major enzymes.
03:38
Galactose is turned into galactose 1 phosphate through galactokinase.
03:44
Galactose 1 phosphate has that enzyme GALT
which then turns it into glucose 1 phosphate
and then we can metabolize the galactose.
03:53
Remember that the galactose, the sugar in milk,
is a galactose plus a glucose stocked together.
04:00
Lactase breaks those apart and then for the galactose,
we use this pathway to metabolize it.
04:06
In patients with galactosemia,
they have a defect in one of these two enzymes.
04:11
Galactokinase deficiency is very rare, we almost never see it.
04:17
Those children typically have a milder course.
04:20
But GALT deficiency is not too uncommon,
and we do see periodically patients with GALT deficiency.
04:27
GALT deficiency usually presents once milk is introduced.
04:33
As you can imagine, milk is introduced essentially right at birth.
04:37
So we screen for galactosemia in the newborn screen
so that we can prohibit the child from getting milk
once they're born if they have this problem.
04:49
We need to give them a special formula that does not have galactose in it.
04:55
Patients where they are not picked up will develop failure to gain weight,
vomiting, lethargy, jaundice, hypoglycemia,
and this is key for your exam, cataracts.
05:09
Exams love to mention cataracts.
05:11
These children can also develop renal failure.
05:14
So obviously, screening for these diseases is very important.
05:18
Even if effectively picked up on the newborn screen
and a rapid intervention is made,
these children can still have problems over time.
05:28
They can develop speech delay, ataxia, gonadal failure, problems can happen.
05:33
But their course is much better
if we can make a dietary intervention early in life.
05:38
Very rare, but we can see hereditary fructose intolerance as well.
05:44
This generally presents once fruit is introduced.
05:47
These children can't metabolize fructose well.
05:50
They generally would develop an increased pyruvate and lactate
which leads to a metabolic acidosis.
05:57
These children can develop abdominal pain, nausea, vomiting.
06:00
They can have a severe hypoglycemia as well,
which ironically, is not relieved by a fruit juice.
06:06
They can develop lethargy, seizure, and diarrhea.
06:11
So these children really need to avoid fructose in their diet.