Megaloblastic Anemias

by Carlo Raj, MD

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    00:01 I haven’t gotten into non-megaloblast yet.

    00:02 Now, these are the common B12 and folate that you need to know, deficiencies.

    00:06 However, there is a couple of others that you have to know of.

    00:11 The other megaloblastic diseases that you must be familiar with or current day boards in practice, one's called orotic aciduria.

    00:18 Orotic aciduria.

    00:20 It’s an autosomal recessive disorder.

    00:23 And what happens? Well as the name implies, you’re not able to convert your orotic acid into UMP, uracil.

    00:32 Interesting, huh? What do you mean? Well, the name says orotic aciduria which means that I have accumulation of orotic acid in your urine.

    00:41 Fantastic! Why? Well, you end up missing an enzyme called UMP synthase.

    00:47 Clear? So if you’re missing the enzyme or synthase of UMP, then you’re stuck in the form of orotic acid.

    00:54 That must be clear.

    00:56 What is this part of? It’s part of your de novo pyrimidine synthesis pathway.

    01:01 What are we dealing with? Megaloblastic anemia.

    01:04 Those of you knew about B12 and folate, fantastic.

    01:07 We’ll go into much greater detail.

    01:09 However, the other important megaloblast that we’re looking at here, still under the category of macrocytic.

    01:17 I haven’t touched non-megaloblast yet.

    01:19 I’ll talk to you about that in a second.

    01:20 Now, presentation becomes important.

    01:22 Here is a child and failure to thrive, there might be developmental delays and absolutely refractory to B12 and folate treatment.

    01:31 What does that mean? That means that megaloblasts are here, you find them on your peripheral blood smear.

    01:36 And, well, B12 and folate is not going to help you replenish the UMP synthase, right? So it’s refractory.

    01:46 Next, a very important point, pay attention.

    01:48 There is no hyperammonemia.

    01:53 There is no hyperammonemia.

    01:55 What does that mean? Well, there is another important biochemical pathology that you need to know.

    01:58 It’s called ornithine transcarbamylase deficiency.

    02:03 So, the enzyme here that is missing is called UMP synthase.

    02:09 The condition that we are referring to, at this point, is orotic aciduria.

    02:12 There is another important enzyme deficiency that you need to know of.

    02:16 That’s ornithine transcarbamylase.

    02:19 In that deficiency, you’re also going to find increased orotic acid.

    02:23 However, you will find hyperammonemia.

    02:28 Be very familiar with the differences between these two orotic acidurias.

    02:33 Two different enzyme deficiencies resulting in different concentration of your ammonia within the blood, within the blood Treatment: Well, it was refractory to B12 and folate.

    02:43 Look for that.

    02:44 That should clue you in.

    02:45 You see no hyperammonemia, this will then indicate you have UMP synthase deficiency or defect.

    02:53 What are you going to do? You’re going to bypass.

    02:57 You’re going to bypass this type of enzyme with its catalytic activity.

    03:01 And so therefore, it’s called uridine monophosphate.

    03:04 And this is then used to bypass the enzyme.

    03:06 And so therefore, you continue having pyrimidine synthesis.

    03:10 Is that clear? The bottom line is this though, if you do not have pyrimidine, you don’t have DNA.

    03:14 If you don’t have DNA, then you don’t have proper formation of your cells.

    03:19 If you don’t have proper maturation of your cells, what is that called in your bone marrow? Good.

    03:24 Megaloblasts.

    03:27 That is one other megaloblastic anemia that you need to know.

    03:29 So now, there are 3.

    03:30 Let’s take a look at the fourth one.

    03:33 The fourth one is called Diamond Blackfan anemia.

    03:36 Who is this patient? Rapid anemia within the first year due to, well, it’s the fact that unfortunately for unknown reasons lot of times, Diamond Blackfan anemia used to come under and that some of you might know this under normocytic non-hemolytic anemia because of what we are seeing here.

    03:53 But now, under current clinical or current day practice, it's the fact that we do know that you do not have proper maturation of your erythroid progenitor cell.

    04:01 Are we clear? So the erythroid progenitor cell within the bone marrow is not being properly matured, what do we have? Good.

    04:08 Megaloblasts once again.

    04:10 What else do we have? Well because you don’t have proper erythroid maturation, you are going to have increase hemoglobin F.

    04:18 Which is what? Fetal.

    04:20 But total hemoglobin, in fact, is going to be decreased.

    04:22 What else does the patient have? The patient has short stature.

    04:26 There will be craniofacial anomalies, especially in the upper extremity, something called triphalangeal, 50% of your patients.

    04:33 Fascinating! Know it.

    04:35 It’s another megaloblastic anemia that you need to be quite familiar with.

    04:39 There are 4 now.

    04:40 B12 and folate go together, we’ll be spending a lot of time with that.

    04:43 But please don’t forget about orotic acidurias and then Diamond Blackfan.

    About the Lecture

    The lecture Megaloblastic Anemias by Carlo Raj, MD is from the course Macrocytic Anemia – Red Blood Cell Pathology (RBC).

    Author of lecture Megaloblastic Anemias

     Carlo Raj, MD

    Carlo Raj, MD

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