This week’s episode of Holby City saw Xavier identify Gaucher’s Disease in a rather battered martial artist. Here we explain the what, the how, and the why of this diagnosis.

Gaucher’s Disease is the most common of the lysosomal storage diseases. Lysosomes are little sacs of degrading enzymes present in your cells, and, when these do not function correctly, you develop a defect in your metabolism.

One of these lysosomal enzymes is the horribly long-named, glucocerebrosidase. Its job is to break down an essential molecule called glucocerebroside, which is present predominantly in white blood cells.

Gaucher’s is an autosomal recessive genetic disease, which means that each parent passes on one mutated copy of the gene involved – glucocerebrosidase. These altered copies (alleles) of the gene result in faulty versions of this vital enzyme, which then no longer degrades glucocerebroside. The outcome? Glucocerebroside accumulates within the cells. These once normal white blood cells turn into the aptly named ‘Gaucher cells’, which have damning implications for the human body.

Now this glucocerebroside and these Gaucher cells can do several problematic things, but, as we saw in the episode, they can lead to bone wasting and bone fractures! The sequence of events between Gaucher’s and bone problems hasn’t quite been determined, however it may be something to do with those dastardly transformed white blood cells.

Using imaging techniques, scientists have confirmed that Gaucher cells infiltrate deep into the bone marrow, where they displace healthy bone cells. By pushing the contents of bone around, this invasion can lead to blockage of local blood vessels, or even blood clots. These both mean that bone cells are later starved of oxygen, resulting in cellular death and the wasting away of the bone. That cannot be nice for Xavier’s poor patient!

What’s more, the build-up of glucocerebroside seems to activate or ‘supercharge’ the white blood cells, whose normal roles involve fighting off foreign invaders. This leads to the Gaucher cells rolling out all sorts of inflammation-causing molecules.

Why is this a concern? Well, bone tissue is all about balance. In the bone, there is a natural equilibrium between two different cell types: osteoblasts, which produce new bone, and osteoclasts, which eat up all the old bone. These cells work together to ensure that the total bone mass remains mostly stable over time. But, with Gaucher cells pumping torrents upon torrents of inflammatory molecules into the tissue, the osteoclasts are triggered to go into overdrive. They remove more bone and more bone and more bone…

Until, eventually, say it were pulled around in a Judo spar, it would snap in two.