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