Timothy Craig is a doctor of orthopedics and a leading clinical researcher in the field of allergy and immunology. He describes the biochemical differences between the three types of hereditary angioedema.

There’s three types of hereditary angioedema. Actually, we’re not supposed to call it type 1, type 2, and type 3. We can call the first two hereditary angioedema type 1. That is the most common by far — probably about 80%, 75%, 85% of cases are of type 1.

In that, what happens is they don’t make a protein that’s called C1 inhibitor. And that C1 inhibitor, what it does, it shuts down factor XII from being activated. So that whole cascade that leads to bradykinin is shut down.

There’s also a type 2. These people make protein, but what happens is the C1 inhibitor is dysfunctional. It doesn’t work well. So the same thing happens. It doesn’t prevent the activation of factor XII, nor the activation of kallikrein, nor the production of bradykinin, and thus they get recurrent swelling, like you see in the hereditary angioedema.

Now there’s a third type, but we can’t call that type 3 for some reason. It’s instead called hereditary angioedema with normal C1 inhibitor. This is a very difficult disease state. We group it with type 1 and type 2, but some of those people who fall under hereditary angioedema with normal C1 inhibitor really don’t even have activation of the swelling from bradykinin. Some of them do.

But there’s a lot of different genetic abnormalities. I think right now, as of the last month or two, there’s now nine different genetic types. Some of them act just like type 1 and type 2. Some of them, like I mentioned, don’t use bradykinin, and a couple of them even kind of differ in how they present themselves as a disease.

So those three types are slightly different, but right now, until further changes in what we call that group of people with hereditary angioedema with normal C1 inhibitor — until we redefine or classify that, right now, there are three types, and they kind of appear very similar.