Robin Ely, MD, explains the three types of Gaucher disease and how the condition affects the body. She talks about the enzyme that’s missing in people with Gaucher, how it causes harmful buildup in cells, and why that leads to symptoms. Ely uses simple examples to help explain how the disease works and why understanding it is important.
Transcript
There are three types of Gaucher: adult type 1, which is found in children but we consider it an adult disorder; an infantile disorder, which is type 2; and type 3, which is found in small children but also these individuals can grow up.
The type 1 only affects the body, or at least we thought that. Type 2 is a very severe disorder, and type 3 affects the body and the brain.
Now, how does this work? Well, first of all, I want to point out to everyone that our understanding of this disease — and everything else, actually, in the world — is evolving.
So it was originally thought that this disorder and its symptoms were caused by the fact that this enzyme is deficient. And because it’s deficient, the normal turnover — the normal metabolism, specifically of lipids (which are fatty molecules) — gets blocked. And because it gets blocked, certain lipids build up. And when they build up, it becomes toxic.
If you think of a stream that’s flowing versus a still, little creek, you’ll see in a still, little creek, algae and other stuff will develop. But in a flowing stream, it doesn’t have a chance to take hold. So this was what originally the thought was — that all of the symptoms are caused by this.
But actually, that’s not true because this enzyme, glucocerebrosidase — it’s called for short GCase, or some people call it G-C-ase — it turns out that this enzyme is a trafficker, a regulatory enzyme that regulates molecules going through the recycling center of the cell. And that center is called a lysosome.
“Lyso” is Latin for break it up, break into small pieces. “Ome” is a body that does something. So breaking up: lysosome. So think of this as being the recycling center of the cell. And every cell has lysosomes.
The body’s always metabolizing — every second. Thousands and thousands of chemical processes are going on. When those processes happen, there’s a breakdown that needs to happen. Break down, recycling, rebuilding proteins — all the molecules that we need for this body.
And when those proteins particularly don’t get to break up, they build up. And they start — just like when you see algae growing together in a creek — they start to glob together. And when they glob together, they interfere with the normal functioning of the cell. They actually interfere with signaling.
All of our cells are always signaling to each other. That’s the sort of electric aspect of our bodies. And that signaling starts interfering with all kinds of things, and it starts causing symptoms.
