Megaloblastic Anemias

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.