Proximal Convoluted Tubule (PCT): Hartnup Disease

by Carlo Raj, MD

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    00:01 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.

    00:16 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.

    00:25 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.

    01:19 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.

    01:36 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 dimentia, dermatitis, diarrhea, death. Hold on to everything that I just said. I am going to reinforce this on the next next slide.

    02:09 Now, amino acids, they are then retained in the intestine. Let me finish this real quick.

    02:17 In the intestine, change gear. You are not able to take up tryptophan. That's the problem.

    02:22 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.

    03:27 Now with hartnup, we have most patients were asymptomatic, pellagra-like skin eruptions.

    03:33 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's that neurologic deficit being caused by? B12 deficiency.

    04:31 B12 deficiency, you have methylmalonic aciduria and you also have megaloblastic anemia.

    04:38 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.

    06:07 Take a look at this cartoon. You will form clear hexagonal crystals, colorless.

    About the Lecture

    The lecture Proximal Convoluted Tubule (PCT): Hartnup Disease by Carlo Raj, MD is from the course Diseases of the Nephron.

    Included Quiz Questions

    1. Vitamin B3
    2. Vitamin B1
    3. Vitamin B12
    4. Vitamin B5
    5. Vitamin B2
    1. Pellagra-like skin eruption and photosensitivity.
    2. Anaphylaxis
    3. Polyuria
    4. Paroxysmal nocturnal dyspnea
    5. Pain
    1. Colorless hexagonal crystals
    2. Envelope-shaped crystals
    3. Rhomboid crystals
    4. Coffin lid–shaped crystals
    5. Dumbbell-shaped crystals

    Author of lecture Proximal Convoluted Tubule (PCT): Hartnup Disease

     Carlo Raj, MD

    Carlo Raj, MD

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