and the defect in the fact that you cannot properly
take up these particular amino acids. Hartnup,
autonomal recessive. Take a look. Impaired
transport of trytophan, hartnup, and other
neutral amino acids. What are these? Well,
at least have a couple in mind, such as leucine, isoleucine.
Now stop there for one second. When this is
an inherited disorder, it means that anywhere
in the body that you are supposed to take
up that particular substance, you cannot.
So not only are you not able to properly reabsorb
tryptophan from the proximal convoluted tubule,
take a look please, you cannot take it up from
the small intestine. Now both of these are then
going to give you interesting issues. Let
us do the kidneys first. If you are not able
to properly take it up from the kidney, then
there goes your tryptophan. Guess which you
need tryptophan for clinically so that, you
know sometimes, you know so much, you do. You
know so much for then you have to organize
your thoughts and you can come with all kinds
of combination, lot of times it is about seeing the
patient in which it finally tells you "Oh!
that is what's going on." For example, we all
know about tryptophan. We all know that is
part of 5-HT, 5-hydroxytryptamine. That is
serotonin. Let it go. Please let that go.
What you truly need here to clinically diagnose
your patient with tryptophan is that tryptophan
is also a precursor for niacin and that is
how your patient is going to present. Are
we clear? So when you talk about hartnup,
first and foremost, your focus is on tryptophan.
Next, tryptophoan, you want to think of it as being a precursor
for which vitamin? Well this is going to be vitamin
B3. What is B3? Niacin. Now you know or you should
know when you have niacin deficiency, what
is the name of that disease? Pellagra. And
when you think about Pellagra, what does that
mean to you? What letter comes to mind? D,D,D,D
mean to say dimensia, dermatitis, diarrhea,
death. Hold on to everything that I just said.
I am going to reinforce this on the next slide.
Now, amino acids, they are then retained in
the intestine. Let me finish this real quick.
In the intestine, change gear. You are not
able to take up tryptophan. That's the problem.
So that tryptophan remains within the intestine.
Guess what it turns into? Take a look. It
turns into a neurotoxin. Unbelievable this
patient will have seen as toxicity. So what
kind of things you are looking for in your
patient? Tryptophan is the precursor for niacin,
stop there. The fact that you have niacin
deficiency now is this complete official pellagra?
No. It is the fact that tryptophan
is missing. So you will have components of
pellagra, which is the most important component?
It is the dermatitis. The pellagra-like eruption
and photosensitivity. Are we clear? Along
with neurotoxicity and you are thinking about
tryptophan, no doubt, clinch your diagnosis
is going to be hartnup. You bring into play
the kidney. You can take up the tryptophan,
niacin, pellagra-like issues especially dermatitis
and photosensitivity in neurotoxicity, you
cannot miss this diagnosis. Let us move on.
Now with hartnup, we have most patients were
asymptomatic, pellagra-like skin eruptions.
Take a look at this patient here. See that skin.
That is the photosensitivity and pellagra-like
eruption, the skin. What else do you think
this patient is feeling or expressing? Maybe
perhaps not because they might have neurological
deficit. They might have cerebellar ataxia,
psychiatric symptoms, skin issue, neurotoxicity
high in your differential, hartnup. Are we clear?
And how do you confirm this? I am going to
leave this tryptophan from the urine. How
could you miss this diagnosis if gross aminoaciduria?
Are you clear? So now be careful with the
term aminoaciduria. Correct. The few differential,
let me give you another one. There is something
called subacute combined degeneration. Now
pay attention here. You know this. Subacute
combined degeneration that also gives you
cerebellar ataxia, but that will give you
MMA, methylmalonic aciduria. So what is statin
neurologic deficit being caused by? B12 deficiency.
B12 deficiency, you have methylmalonic
aciduria and you also have megaloblastic anemia.
So you have a point ladies and gentleman now
we are doing pathology. No joke. This is
medicine. Your job, so that you are to be highly
successful on your rotations and on your boards
is make sure that you come up with two or
three differentials for many of the symptoms
as possible and then you clearly distinguish
one from the other so that you are not just
compartmentalizing. We cannot do that anymore
and we haven't been. Okay. This is aminoaciduria,
skin infection, neurotoxicity, hartnup. Let
us continue. we you have cystinuria. Right
off the bat, I want you to take a look at
the green box. And we have nicely known mnemonic that
is called COLA. Autosomal recessive. You cannot
take up your cysteine, ornithine, lysine,
arginine. Your focus should be on cysteine,
a dibasic amino acid and this may then predispose
you to cysteine stones. So the other time that
we will repeat this is when we get into kidney
stones. Okay. Now with the cysteine stones,
you end up on urinalysis forming these beautiful
crystals. They are hexagonal. It is unreal,
really is. One would think yourself that "I
actually feel jealous that I can form such
crystals in my urine." Don't be because this
is a patient who is not able to take up cysteine
and may be perhaps some of these other amino
acids. Where am I? PCT. Recurrent renal, ureteral,
bladder stones, 24-hour urine collection.
Take a look at this cartoon. You will form
clear hexagonal crystals, colorless.
RTA type II, well where am I? Proximal convoluted
tubule. Bottom line is inside of the picture,