Lessons from Gaucher Disease and MTHFR Deficiency

Second Life: Relay for Life 2007: Angel in the Cherry Blossoms

A friend of mine was diagnosed with Gaucher’s Disease this week. (Gaucher is pronounced the French way, Go-Shay.) For most folk this would be a bad thing. For her, it was a gift. It reminded me of when I finally got my celiac diagnosis. I’d been sick at varying levels for at least 20 years. Finally having a diagnosis and being able to DO something about it was … unimaginable. Imagine eyes raised to heaven, and angels singing with serene beauty. A sense of humble joy, and relief.

Then, for me, finding the MTHFR aspect, and realizing it isn’t entirely clear where the celiac leaves off and the MTHFR begins, or visa versa. They seem to be pieces in the same puzzle, interacting in ways that are not necessarily straight forward. The MTHFR in particular is complicated, since it has been overlooked and neglected by the healthcare system until very recently, and like celiac in the USA, is often overlooked.

Well, surprise! Gaucher has some real similarities to this scenario. Like MTHFR deficiency, Gaucher disease has a very rare and severe (read: deadly) manifestation, AND a milder version often overlooked or misdiagnosed, but often disabling. Both Gaucher disease and MTHFR deficiency involve a genetic profile that creates a lack of an enzyme needed to break down a chemical in the body. Lack of the enzyme and inability to break down the chemical compound means that the body ends up with too much of something it doesn’t need and doesn’t want, and not enough of something it does need. And, for both these conditions, that imbalance then causes a wealth of confusing symptoms and a poverty of health and ease.

For MTHFR deficiency, the enzyme needed is Methylenetetrahydrofolate reductase (MTHFR). (Duh. Obvious.) MTHFR, when you have the right stuff, converts homocysteine (toxic, as in bad for you) into methionine (essential, as in something your body needs). Too much homocysteine is related to a lot of difference diseases, most commonly heart disease, nervous system and psychological diseases, and osteoporosis and fragile bones. Recently, there is research showing that too much homocysteine might be related to a number of cancers. There’s plenty more, but that gives you the idea that this can be trouble.

For Gaucher disease, the enzyme needed is the lysosomal enzyme glucocerebrosidase. That’s a mouthful, but I bet my friend manages to learn to make it roll off her tongue easily in no time! Just as with MTHFR, not being able to break down the chemical, means you end up with too much in your body, and then that causes damage. For Gaucher, instead of getting too much homocysteine, you have too much in the way of glucocerebrosides. What is supposed to happen with the glucocerebrosides is that they are broken down into the sugar called glucose and a fat called ceramide. Your body knows how to use those. But a person’s body kind of chokes on the glucocerebrosides. The cells that are supposed to break them down (a type of white blood cell called macrophages) actually get bloated and confused, and stop doing what they are supposed to do. In case you don’t already know, white blood cells are part of your immune system, so with the macrophages in trouble, that means EVERYTHING is in trouble, but especially the spleen, lungs, kidneys, and often the brain. Talk about scary! Early signs include anemia, easy bruising, bone pain, and easy fractures. Those early signs of Gaucher are coincidentally also sometimes early signs of celiac disease and MTHFR deficiency, BOTH. See why it is so hard to diagnose these things?

Here’s another similarity, but this one between me and my friend’s diagnoses, rather than the diseases. Both both of us, the symptoms we showed were not the expected presentation. We had the disease, but the docs missed it for years simply because what they were trained to look for was different from how it manifested in our bodies. Let me try to say that a different way. The symptoms for both of these come from the build up of the bad stuff in our bodies, but that build up can cause things to break down in more than one way. For most people, certain things break down, but for both of us the stuff that broke down was unusual. These are the kinds of diagnoses that make perfect sense after the fact. Hindsight is always 20/20, right? For my friend, her family had approximately the same symptoms for five generations, and no one ever figured it out. For me, we are less sure, and less clear, but I see echoes of my symptoms in old family stories. I wish I could go back in time and tell my beloved grandfather to change his diet so that he wouldn’t die crippled and in pain.

So with both of us having a disease that didn’t “behave right”, how did we end up with our diagnoses? You know mine — personal genomics. It took those genome scans to give the right clues, and then to combine those with some educated guesses about treatments. For her? Well, guess what? It was personal genomic again! Well, how do you figure that? What a surprise. Or maybe it is no surprise that both of us have become rabid evangelical supporters of personal genomics, especially for anyone with mysterious ongoing symptoms or chronic diseases that just don’t seem to get genuinely better no matter what you do.

Since my friend’s diagnosis, a bunch of us on Twitter have been reading up on Gaucher. I stumbled on this article today, and it set off a lightbulb in my mind.

Sidransky, Ellen. Gaucher Disease: Insights from a Rare Mendelian Disorder. Discovery Medicine October 27, 2012. http://www.discoverymedicine.com/Ellen-Sidransky/2012/10/27/gaucher-disease-insights-from-a-rare-mendelian-disorder/

Here is the sentence that rang like a gong.

“It has become increasingly clear that “simple” recessive disorders provide unique insight into the complexities of common diseases.”

Deeper into the article there is a second similar sentence.

“These rare inherited disorders often offer a unique window into seemingly unrelated diseases.”

You start talking about “seemingly unrelated diseases” with celiac and you end up with a laundry list of associated conditions that cover the entire body and every major organ system. Ditto for MTHFR deficiency. And a lot of the conditions are the same ones. And they are also associated with Hashimoto’s Disease, chronic fatigue syndrome, myalgic encephalomyelitis, miscarriages, preterm labor, osteoporosis, bipolar, schizophrenia, depression, migraines, epilepsy, memory loss, cognitive decline and mental confusion, and simple things like joint pain, and weird things like hidradenitis suppurativa, and … and … well, I could go on a long time. I started to draw up a list once, to try to organize them all, but it was a bit overwhelming.

This article about Gaucher disease was describing the same sort of far ranging connections to other diseases.

“Studies of patients with Gaucher disease have led to unanticipated research directions impacting several distinct medical disciplines. Some notable examples include the link between mutations in the glucocerebrosidase gene and the development of Parkinson disease and related Lewy body disorders, elucidation of the role of glucocerebrosidase in skin barrier function and neonatal viability, and the connection between lysosomal transport and myoclonic epilepsy.”

Like Ellen Sidransky, I am now asking if there might be a significant pattern forming here. How many of our chronic diseases are actually caused by a cascade of events deriving from a simple bit of biochemistry gone wrong in our bodies? For me, this was easily addressed with a change of diet and new vitamins. For my friend it won’t be quite as easy (enzyme infusions), but it is still a LOT easier than all the meds she’s been taking and hospitalizations she’s been going through. Quality of life improvement is unbelievable, at least for me. Her treatment hasn’t started, but I expect the same phenomenal improvement in quality of life (QoL).

On the one hand, part of me says, “Why? Why did it have to take so long? Why was it so darned hard to figure out? Was there a point to all these years of struggle and pain?” On the other hand, I kind of ‘get it’, I can see how difficult it must have been to figure out. I still resent all the docs who tried to convince me it was in my head, but I am also so very very grateful that the personal genomics tests have reached the point where they are more accessible, and CAN help people like me. Like my friend. And hopefully, many many more.

A Few Resources

Gaucher Basics: http://www.childrensgaucher.org/about-gaucher/gaucher-basics/

Genome.gov: Learning About Gaucher Disease: http://www.genome.gov/25521505

Science Daily: Macrophages: The ‘Defense’ Cells That Help Throughout the Body: http://www.sciencedaily.com/releases/2010/08/100826141232.htm

NINDS Gaucher Disease Information Page: http://www.ninds.nih.gov/disorders/gauchers/gauchers.htm