Simple Guide to Gauchers Disease


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An informative, simple but mind-provoking guide to Gauchers disease was given by Dr Paul Schofield, Consultant Physician at Addenbrooke's Gauchers Clinic, as an introduction to the Gauchers Workshop in March. Using computer graphics and easy to understand language, Dr Schofield talked his way through what happens inside the bodies of Gauchers patients. The computer images to accompany this talk can be found at Addenbrooke's Gaucher website .

What is blood?

The majority of patients attending clinic end their visit by having a sample of blood withdrawn for further analysis.

This red liquid is placed in several tubes and spun around at high speed in a centrifuge. A centrifuge can be thought of as like a spin-dryer in that it spins very fast and separates the blood in about a 50:50 ratio of straw-coloured plasma at the top of the tube and at the bottom a red mass of blood cells.

We can look in more detail at the blood cell component by taking a sample and placing it on a microscope slide. Chemical dyes can be added and different cell types take up different dyes, which allows us to distinguish between the different cells.

The majority of the cells that can be seen after this preparation are the red blood cells which give blood its red colour and are important for carrying oxygen around the body to the tissues.

A smaller fraction are the sticky platelets which are important in blood clotting. The third component consists of the white blood cells, which themselves can be divided into five main types. The white blood cells act to fight infection and circulate around the body cleaning up in areas of inflammation or infection.

I would like to concentrate on one particular type of white blood cell called the monocyte.

The monocyte is a type of white blood cell which circulates around the body and can then squeeze out of the blood vessels into the tissues. The monocytes that are found within the tissues are given a different name macrophages.

Big-Mac

The word macrophage means 'big-eater'. You can think of these big-eaters patrolling around the tissues, mainly the liver, spleen and bone marrow, eating pieces of material such as old cell membranes and other waste products, just like garbage disposal units.

Gauchers Disease Gives

Big-Macs' Indigestion

What happens to the material that is swallowed by the macrophages? Inside these cells are little bags called lysosomes which can be thought of as being the cell stomachs which digest the swallowed material taken in by the big-eaters.

Within the lysosomes are powerful digestive enzymes, very much like biological washing powder, which can break down the proteins and membranes consumed by the macrophage.

So imagine you are standing in the spleen watching the macrophage approach an old piece of a cell membrane, biting a piece of it and swallowing it.

Then, with your X-ray vision, look inside the macrophage and see the tiny little lysosome bags empty their contents into the stomach of the cell which can then break down the membrane into tiny pieces called molecules.

Lysosomes aid digestion

I can now explain how this fits into Gauchers disease, which is a disorder of the lysosomes. The lysosomes, as I have said, contain many different powerful digestive enzymes.

One particular enzyme is either partially or completely inactive within the lysosomes of Gauchers disease individuals. The enzyme is called beta-glucocerebrosidase.

Imagine what would happen if again you were stood inside the spleen but this time of someone affected by Gauchers disease.

The macrophage could still eat pieces of cell membrane, swallow them, and the lysosomes would empty their contents into their stomach.

But because in this instance one of the important enzymes is missing, not all of the swallowed membrane can be digested and it therefore builds up within these lysosomes.

There becomes a vicious cycle in that the more membrane the big-eater swallows, the more that this rubbish accumulates within the cell which becomes engorged by this material.

The name of the material, a part of the cell membrane, is called glycolipid. Glyco refers to the sugar molecule component, and lipid to the fatty part of the molecule. The particular glycolipid in Gauchers disease is called glucocerebroside.

The defective lysosomal enzyme is glucocerebrosidase. Finally, the macrophage, engorged with undigested glycolipid inside its lysosomes, stops the cell working properly and this is called a Gauchers cell.

Organ Damage

So what is the consequence of having all these Gauchers cells, engorged with undigested glycolipid, within the major organs of the body such as the liver, spleen and bone marrow?

Well, the accumulation of these cells leads to swelling and further damage of the organs so that the spleen can become enlarged, as can the liver. Expansion of the bone marrow can damage the bones themselves and lead to bone disease...continued


Part 2 of this article

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Source: Gauchers News July 1998

© Copyright Gauchers Association 1998