Sunday, April 5, 2015

Sam and Buddy


Here is a story Sam wrote today.  He wanted to play Plants vs. Zombies on the i-Pad for the millionth time, so we told him he needed to write for 30 minutes.  This is what he came up with:

Sam and Buddy  

Buddy was Sam's dog.
Sam loved Buddy.  Buddy was a homeless dog.
He came to me in the woods.  I was taking a walk.


"Do you have a home?" And Buddy said, "Ruff!"

I knew he did not have a home.  I took him home.

The End.






Tuesday, March 31, 2015

Plan B: Rituximab



Today Sam got his first infusion of rituximab.

Let me back up.  Our plan was to try high dose prednisone for 3 months to see whether that could shut down the antibody response that is damaging Sam's kidneys.  Sam was on 30 mg of prednisone daily.  It was terrible.  We have so much sympathy now for anyone who has to take prednisone, especially high doses.

We had heard it could make you ornery, but we still weren't ready for the unpredictable mood swings and tantrums.  It was like Mt. Vesuvius every fifteen minutes.  Sam is a stubborn kid at baseline, but there was a noticeable change on prednisone.  And worst of all, it didn't really work.  He still has really high levels of protein in his urine.  There was a modest decrease that was most likely due to the ACE inhibitor he started taking, lisinopril.  His protein/creatinine ratio dropped from 14 to 5.  And his serum albumin came back up into the normal levels.  But his kidneys are still inflamed and dumping protein like it's going out of style.

There were some benefits to prednisone.  Sam started eating a lot more.  We were able to stop all his night tube feeds, which was nice.  His face definitely got chubbier, with little chipmunk cheeks.  We'll see if those hang around now that we are tapering off.  We are currently down to 10 mg daily, and it will take us another month to get off prednisone completely.

So prednisone didn't work.  That meant we had to move to plan B.  Our nephrologist didn't want to use cyclosporine, which is the usual treatment for membranous nephropathy, because it can be toxic to the kidneys.  This would be especially risky in a child with cystinosis who is constantly at risk for dehydration.  So that left two other options: mycophenolate or rituximab.  Our nephrologist went with rituximab.

Rituximab is an antibody against the cells that make antibodies (wrap your head around that).  It targets the precursors to B-cells.  B-cells are important immune cells that recognize bad guys like bacteria and viruses, and they make antibodies against them.  Sometimes they get confused and make antibodies against things in the human body.  That's how autoimmune diseases like rheumatoid arthritis and Crohn's disease happen.  Rituximab is an effective treatment for autoimmune diseases because it takes out the B-cell precursors.  No B-cells, no antibodies.  Rituximab was actually originally developed for B-cell lymphomas.  In lymphoma the B-cells start proliferating out of control, so rituximab can be given in addition to chemotherapy to get rid of the cancer cells.

Rituximab is expensive, so our nephrologist had to make a special case for Sam to get it.  Then Ashton had to call our insurance and Primary Children's a million times to get the pre-authorization processed.

Since rituximab is given through an IV, Sam had to come to the hospital for his infusion.  We were admitted to the Rapid Treatment Unit (RTU), which is where he stayed after he got his kidney biopsy.  It's like an observation unit for short stays.  Since rituximab is an antibody there is always the risk of an allergic reaction.  To minimize this risk, Sam got benadryl, tylenol and solumedrol before his infusion.  Then they ran the rituximab really, really slow.  Luckily Sam didn't have any reactions to it.

Sam was pretty apprehensive about the IV.  He brought five of his stuffed animal dogs with him for support.  Luckily the IV team got it placed on their first try.  Then it was just room service and movie marathon after that.  He watched Frozen, Matilda and the Nightmare Before Christmas while chowing down on a cheeseburger and Pringles.  We haven't been watching TV at home so this was his opportunity to binge.

The plan from here is to do an infusion once a week for three more weeks.  That will be a full course of treatment, and it should knock his immune system down for three to six months.  We'll track the protein in his urine and see if it slows down in the next month.  If it doesn't work, I don't know what plan C is.

Rituximab has to work.  We'll be praying for that and we appreciate your prayers too.

Monday, December 15, 2014

The Plan


On Thursday we met with our nephrologist.  He spent about an hour going over his thoughts and what the plan is from here.  He is just as baffled by the diagnosis of membranous nephropathy as we are.  He sees it in adolescents, but not in kids Sam's age.  He is fairly confident it's an autoimmune process in Sam.  We are still waiting for the phospholipase A2 antibody test to come back, but he doubts that this is the real problem in Sam.  He thinks it's a drug.

What drug?  The one that is supposed to be prolonging Sam's life by helping get cystine out of the lysosomes.  Cysteamine, also called Cystagon (the short-acting 6-hour pill that Lars is on) or Procysbi (the long-acting $350,000-a-year drug that Sam is on) has a sulfhydryl group on it.  The most common drugs (besides NSAIDs) that have been implicated in membranous nephropathy have a sulfhydryl group, including captopril and penicillamine.  Something about the way the sulfhydryl interacts with proteins in the body triggers an immune response that has downstream effects that damage the kidneys.  This is all speculation, but it's the best hypothesis our nephrologist has.  It's a hypothesis that's impossible to prove, and we can't really take him off the drug anyway.

Everyone with cystinosis takes this drug.  Why hasn't anybody else every developed membranous nephropathy?  Good question.  If you search the published literature for a case of cystinosis with membranous nephropathy, you won't find one.  Our nephrologist is going to write a case report about Sam, to get it on the books.  Just because it's never been published before, doesn't mean it doesn't happen.  Other kids with cystinosis do get protein in their urine.  Usually it's during the teen years, when the kidney is progressing toward needing a transplant.  At that point, people rarely get biopsies.  The doctor just blames it on cystinosis and the patient gets a transplant.  A lot of patients don't routinely get their urine checked, either, so if there is protein in the urine, it is not being detected.  It would be a really interesting study to collect urine samples from a bunch of cystinosis patients to see what the prevalence of albuminuria in the general cystinosis population is . . . I might have to do that study one day.

Enough of the speculation.  What is the plan?  Well, since it's an autoimmune disease, our nephrologist wants to start with prednisone.  We are going to try three months of high dose prednisone to see if we can shut it all down.  Prednisone is cheap and it's been around forever.  Anyone who has ever taken it will tell you it has side effects.  One of the side effects in children is "orneriness."  At least we have something to blame when Sam throws a tantrum!  Another side effect, and maybe a silver lining, is increased appetite.  Sam has only been on the medicine for 4 days, but we can already see this in action.  He shovels in the food, and then comes back for seconds and thirds.  

The other medicine Sam is starting is lisinopril, an ACE inhibitor.  This medicine decreases filtration through the kidney, reducing how much protein leaks out.  It is a blood pressure medicine, so we are starting on a real small dose to make sure Sam can tolerate it.  It can bump the creatinine too, so we have to be really careful when he gets dehydrated.  

We got some more bad news last week as well.  Sam's cystine level came back at 1.99.  It is supposed to be below 1.  His levels have been really hard to control ever since he switched to swallowing pills, and since he started school.  It screwed up our whole schedule.  We went up on the dose of Procysbi, and we are also stopping night feeds, since the Boost formula negatively affects Procysbi absorption.  It's nice for Sam to not have to do night feeds anymore, but we do worry about him getting enough calories.  Hopefully starting the prednisone will balance that out.

So that's the plan. Prednisone for 3 months, lisinopril probably indefinitely.  We'll be checking labs every 2-4 weeks and hopefully get things under control.  If prednisone doesn't work, we'll be moving to the next line, which would probably be rituximab and cellcept.  Our nephrologist said he would never use cyclophosphamide or cyclosporine in someone Sam's age (sigh of relief).  Too many side effects.  He is actually pretty optimistic that we can get the disease into remission, which is reassuring.  We'll just have to wait and see.  

Thanks for all your prayers and kind words of support.  They mean a lot.   

Friday, December 5, 2014

Membranous Nephropathy



We got the preliminary results back on Sam's kidney biopsy from the nurse practitioner.  We still haven't heard back from our nephrologist (!!!), so we have a lot of unanswered questions.  It was not what we were expecting at all.  The most common cause of nephrotic range proteinuria in kids is minimal change disease, something that responds pretty well to a course of steroids.  That would've been "good" news.  The bad news we predicted was that the biopsy would show scarring from cystinosis, something irreversible and an indicator of progressive kidney dysfunction, likely requiring transplant earlier in life.  What we found was a whole new version of bad news.  

The pathologist found membranous nephropathy, a microscopic pattern that makes doctors cringe with painful memories of cramming for exams.  Membranous nephropathy is certainly on the list of things that cause protein in the urine, but it wasn't on our list.  It's fairly uncommon in adults, and from what I've read, it's pretty rare in children.  So how about that? Sam has two rare diseases. 

What causes membranous nephropathy?  The most common cause is "idiopathic," meaning doctors don't know exactly.   Other causes include lupus, diabetes, certain drugs including gold salts and NSAIDs, hepatitis B, and some cancers.  But what causes it in kids?  The most common cause in children is the autoimmune variety.  That means Sam's body has probably made antibodies against something in his kidneys.  A possible target is the phospholipase A2 receptor.  Sam is getting tested for that antibody today.

Autoimmune diseases are treated with immunosuppressant medications.  Membranous nephropathy is treated with cyclophosphamide, a chemotherapy drug, or tacrolimus, cyclosporine or mycophenolate, all drugs commonly used in organ transplants.  We will also most likely have to use an ACE inhibitor too, to help reduce protein leakage.  New medications with new side effects, some of which are pretty terrible.  With therapy, about half of cases will go into remission.  About a third of cases go into remission and then relapse later.  The rest are progressive, leading to end-stage renal disease.

So you can see how this is bad news.  Before we were "just" battling a rare genetic disease, with a glimmer of hope that it could be cured with stem cell transplant.  Worse case scenario before was that Sam would still have to get a kidney transplant, but we were going to beat the odds.  Now he has something else attacking his kidneys -- his own immune system.  Now if he gets a kidney transplant, there's a chance the antibodies will attack the new kidney too.  

We were finally feeling adjusted to our life with cystinosis.  This is the kind of situation that makes you look up into the heavens and ask, "Anything else?"  We have always tried to be optimistic, but this feels a little like running into a brick wall.

The silver lining is that there wasn't a lot of scarring.  There was some "focal" glomerulosclerosis, but not widespread.  And there weren't a lot of cystine crystals, either.  So I guess we can feel okay about the efficacy of Procysbi.  We had been worried about that, blaming ourselves for getting Sam in the trial when he was so young, before it had been tested in children.  At least we can put that to rest.

Sam is a fighter.  Literally, you should see him beat up Lars.  This is the biggest curveball yet in our journey with chronic disease.  If there's one thing I have faith in, it's that Sam is not going to let some histologic mouthful stop him from living life to its fullest.  He can still become a ninja, doctor, pilot, spy, or whatever else he comes up with next.  

Tuesday, November 25, 2014

Kidney Biopsy



At Sam's last nephrology appointment, everything was looking great.  His height and weight had moved up percentiles into the 40s.  His electrolyte levels were stable.  His albumin was a little low, but still in the "normal" range.  It had been low a few months ago too.  Our nephrologist ordered a urine test, and this showed protein in the urine.  A LOT of protein.  This took us completely by surprise.

We checked a first morning urine again, hoping it was a fluke.  The massive proteinuria persisted.  We waited almost two weeks to hear back from our nephrologist.  In the mean time, we panicked.  What did this mean?

Cystinosis is a disease of the kidney tubules, which normally reabsorb electrolytes, glucose and small proteins from filtered urine.  It is normal in cystinosis to have leakage of small proteins, but these proteins aren't even detected by normal urine dipsticks.  Sam is losing albumin in his urine, which suggests that the glomeruli are damaged.  The glomerulus is the part of the kidney that filters blood to make urine.  The glomerulus can be damaged by a lot of things.  The most common diseases in kids are minimal change disease and glomerulonephritis.  Other causes include autoimmune diseases, like lupus.  

We hadn't heard of other kids with cystinosis having nephrotic range proteinuria before.  We knew that proteinuria occurred with end stage kidney disease, before transplant time.  Usually the proteinuria is more gradual, however.  Did this mean Sam was going to need a transplant sooner?

It's possible that Sam has something completely unrelated to cystinosis causing the proteinuria.  But it's also possible that the cystine crystals have damaged the glomeruli too.  But why would this happen?  We never miss a dose of Sam's medications.  We are neurotic about that.  We do have some concerns about Procysbi's efficacy compared to Cystagon because Sam did have a really high cystine level several months back.  The effect of Procysbi seems to be more unpredictable depending on what you eat and how strictly you follow rules about eating before and after.

We talked to Dr. Grimm about it via e-mail, and he said that it's possible Sam had sustained enough damage to his kidneys when he was a baby, prior to diagnosis, that now as he grows bigger his remaining functioning nephrons can't compensate.  He may actually be showing signs of "hyperfiltration injury."  He said that sometimes no matter how strict you are with giving medicines on time, the disease just progresses.  It seemed to us that if the cystinosis is progressing, however, then Sam wouldn't be growing so well, and his other electrolytes, like potassium and bicarbonate, would be dropping too.

We heard back from our nephrologist, Dr. Nelson, and discussed the options.  He was baffled by the degree of proteinuria as well, and thought the best thing to figure out what is going on was to get a kidney biopsy.  This meant a short stay in the hospital.  We prepped Sam for it a couple weeks out by telling him he got to have a sleepover at the hospital.  A week before the biopsy he packed a suitcase with pajamas, underwear and movies.

On Friday morning Sam walked in wearing his ninja costume, carrying his suitcase and his stuffed dog, Piratesbandofmisfits (Pirates for short).  First he had to get labs and an IV.  Since he needed to have an empty stomach for the procedure, we had to hydrate him for a few hours before because he drinks a lot of water.  He was pretty nervous about the IV, but once it was in, it didn't seem to bother him.  Ashton's mom watched Lars all day, which was really wonderful so we could both be with Sam.  Around noon Sam was brought back to ultrasound, where he got some versed and ketamine.  Dr. Nelson performed the biopsy and took 4 small core samples.  Usually they do 3, but he wanted to prepare one extra sample to look for cystine crystals in the glomeruli.

The procedure went smoothly without complications.  Sam was taken to the RTU observation unit where he had to lie flat on his back for 6 hours.  We surprised him with a new stuffed animal, a big golden retriever from Ikea that he had been wanting for months.   When Sam saw the new dog he was still waking up from the anesthesia, so he was a little giddy and confused.  "Wait, wait, wait, wait," he repeated with disbelief.  "When did you buy that??"  He named the dog Ivy, after his IV, and then Ivy Scooby-Doo, and eventually he shortened it to just Scooby-Doo.  




Sam spent the rest of the day watching a Scooby-Doo marathon and ordering food from the room service.  He ate an entire personal pizza and serving of french fries for lunch, and a corn dog and fries for dinner.  So healthy.  We had to collect all of his urine to monitor it for significant bleeding.  It started out pretty yellow but by night time it was strawberry colored.  He had some soreness at the biopsy site which got better with tylenol.  He did great overnight and was discharged the next morning.  He was jumping on his hospital bed before he left.  Dr. Nelson told him to avoid rough housing, wrestling and even recess for the next 10 days to make sure he doesn't develop any bleeding at the biopsy site.

So now it's just a waiting game for the pathology results. We are really hoping they find something else on the biopsy, like minimal change disease, that we could just treat with steroids for a while.  If all they see is glomerulosclerosis, or scarring of the glomeruli, then we'll have to accept that it's the cystinosis causing more kidney damage.  The only treatment for that is an ACE inhibitor like enalapril to reduce filtration through the glomeruli, which also decreases how much protein leaks out.

Thanks to everyone who visited, sent messages of support and asked how Sam is doing.  We are fortunate to have such a great community of friends and family.  Now please put your blood types in the comments.       



Wednesday, November 19, 2014

Our friend, Macey




 She is just so darn cute.



Dress Up

First, he told me to get the dress ups.  Then, in his bossy voice, he told me to get the camera.  I started snapping photos and he said, "give me candy corn".

















Halloween was this good







hedgehog, batman, monster, phantom of the opera, ninja







Thursday, October 16, 2014

Dr. Cherqui and the Amazing Lysosome-Swapping Macrophage!

Dr. Stephanie Cherqui has previously shown that if you transplant hematopoietic stem cells (HSCs) into cystinosis mice, you get stem cell engraftment with reduction in cystine in the tissues and preservation of organ function.  She is currently working on safety studies so that we can move forward with human trials with autologous HSC transplant for patients with cystinosis. 

But how do the stem cells actually fix the cystinosis cells?  Dr. Cherqui and her lab recently published a paper in Stem Cells revealing the mechanism.  Several hypotheses had been suggested.  Do the stem cells turn into new kidney cells, or do they fuse with the diseased cells to create a functioning hybrid?  It turns out it’s neither.


First you have to remember that cystinosis is a disease of the lysosome.  The lysosome is like the recycling plant of the cell.  It takes up old proteins, digests them into amino acid building blocks, and spits them out through transporter pumps to be reused.  

Cystinosin is the transporter that pumps out cystine, and if it is broken, like it is in cystinosis, then the cystine can’t get out of the lysosome. Cystine builds up, damaging the lysosome and the cell. Cystinosin is probably involved in a lot of other cellular functions too, which explains why giving people cysteamine doesn’t cure cystinosis.  You can’t just get rid of cystine; you have to replace the Cystinosin transporter somehow.

Dr. Cherqui showed that most of the stem cells turn into macrophages after transplantation.  Macrophages are a type of immune cell, and their name literally means “big eater.” Macrophages like to munch on bacteria, and they also clean up the big mess made by the other immune cells that are fighting viruses and bacteria.  Since the macrophage is designed to clean up, it has lots of LYSOSOMES!   

MACROPHAGE!

Dr. Cherqui’s latest research shows that these helpful macrophages respond to a distress call from the sick cystinosis cells by creating little tubes, called tunneling nanotubules (TNTs), through which they share lysosomes with the sick cells.  Healthy lysosomes with the Cystinosin transporter move into the cystinosis cells, and the sick lysosomes move out of the cystinosis cells and into the macrophages.  It’s almost like a lysosome transplant!

In the movie below, posted with Dr. Cherqui's paper in Stem Cells, you can actually see the lysosomes (the little green dots) leaving the macrophage through the tunneling nanotubules to the cystinosis cells, which are red.  So cool! 



This research could have big implications for other diseases.  Cystinosis is just one of fifty lysosome disorders.  Other lysosome disorders include Tay-Sachs disease, Fabry disease, Niemann-Pick disease, Gaucher disease and metachromatic leukodystrophy.  What if HSC transplantation could swap out the broken lysosomes in these diseases?  It's also interesting to note that lysosomes aren't the only organelles that move across the tunneling nanotubules.  Dr. Cherqui and other researchers have also noted mitochondria making the trek.  Mitochondria are the "powerhouse" of the cell, where most of the energy required for cellular function is generated.  There are many mitochondrial disorders, and it is possible that HSC transplantation could be used to treat these as well.  The cure for cystinosis could be the cure for a whole host of genetic diseases!   



Thursday, October 9, 2014

How to Cure Cystinosis

I still remember in 2011 when Ashton came home from the Cystinosis Research Foundation Day of Hope conference and told me there was a scientist who had cured cystinosis in a mouse model with hematopoietic stem cell transplant.  Hematopoietic stem cells, or HSCs, are the stem cells in the bone marrow that develop into blood cells, including the red cells that carry oxygen, and the white cells that make up our immune system.  I had just finished my hematology block in medical school, and what Ashton was telling me sounded preposterous.  Bone marrow transplants are definitely effective for certain blood diseases like multiple myeloma and immunodeficiencies, but it didn’t make any sense that stem cells destined to become blood cells could repair damaged kidney, liver, muscle and thyroid tissue.  Boy, was I wrong!


Dr. Stephanie Cherqui.  Photo from Cystinosis Research Foundation.

In 2009 Dr. Stephanie Cherqui showed that if you give a cystinosis mouse a bone marrow transplant, it leads to reduction of cystine in all organs, including the cornea, and preservation of kidney function.  She showed the same thing in cystinosis mice who received a HSC transplant.  The effect was still present 15 months after the transplant.  This paved the way for FDA approval for a bone marrow transplant trial for cystinosis, which is still waiting to enroll its first patient.

The idea of curing a genetic disease like cystinosis with an allogeneic bone marrow or HSC transplant is pretty exciting.  But bone marrow transplants are not risk-free.   The biggest complication is graft-vs-host disease, where the transplanted bone marrow cells actually attack the recipient, leading to severe skin, liver and gastrointestinal disease.  You also have to kill the patient's bone marrow before transplant with chemotherapy, putting the patient at high risk for infection.  Thankfully Dr. Cherqui has found a way around this.

Rather than give the person with cystinosis someone else's hematopoietic stem cells, why not take some blood from the cystinosis patient and genetically modify the stem cells to express the correct Cystinosin genes, and then give them back as an autologous transplant?  This way you already have a perfect match.  You basically eliminate the risk of graft-vs-host disease, and you don't have to use the same intensity of chemo to suppress the bone marrow prior to transplant.  Sounds pretty great, huh?

In 2013, Dr. Cherqui published research showing she had found a way to deliver the correct Cystinosin gene to stem cells with a virus, specifically a lentivirus.  The virus goes into the cell and copies its DNA, including the correct Cystinosin gene, into the stem cell's DNA.  The stem cells were then transplanted back into the mice from which they were taken, and these cystinosis mice had the same reduction in cystine and organ preservation as the mice that got allogeneic HSC transplantation.  


With these amazing results, Dr. Cherqui has now moved toward clinical trials in humans, and is currently working on safety studies for the FDA.  Hopefully in the next few years there will be a trial for autologous HSC transplant in actual patients.  All of this is possible because of the Cystinosis Research Foundation, who has funded Dr. Cherqui's research.  We are so grateful for Dr. Cherqui's tireless dedication. I won't be surprised when she wins the Nobel prize. The cure is coming!

Wednesday, May 21, 2014

the year 2014 so far

Here is a little movie mashup of some of the highlights from the last few months. 


Wednesday, April 30, 2014

THANK YOU to... Hip & Humble


Dear Friends and Family, 
The upcoming silent auction for Sam's Hope for a Cure is going to be AWESOME because Hip & Humble just donated a $50 gift card!  My mother-in-law, Leslie, introduced me to Hip & Humble shortly after Stephen and I were married.  I LOVE IT!  I feel creatively inspired every time I enter the store.  The cute alphabet cards from Sam and Lars' room are from here.  Check out their stores.

Salt Lake City, Utah

1043 East 900 South

Bountiful, Utah

559 West 2600 South

Sandy, Utah

676 East Union Square (9400 South)

We're on Apartment Therapy! Check it out.

http://www.apartmenttherapy.com/sam-lars-happy-handmedown-room-my-room-202867

Wednesday, April 23, 2014

Vitamin D and Muscle Wasting


Dr. Robert Mak, a pediatric nephrologist, gave a talk at the 2014 CRF family conference about the effects of Vitamin D on muscle wasting in cystinosis.  His talk generated a lot of excitement and interest, so I thought it would be worthwhile to break it down here.

Muscle wasting is one of the major complications of cystinosis, and it is typically seen later in life, in the second and third decade.  Cystine accumulation damages muscle cells.  The muscles predominantly affected are swallowing and limb muscles.  Many patients with cystinosis have trouble swallowing, especially as they get older, and the deterioration of these muscles can lead to aspiration of food and saliva into the lungs, which can cause serious complications, even death.  Wasting of the limb muscles can cause weakness in grip strength and affect dexterity, as well as exercise endurance.

Currently, there are no great therapies for muscle wasting.  Cysteamine depletes the cystine in the muscle tissue, but even patients taking cysteamine eventually develop muscle wasting.  Many cystinosis patients take carnitine supplements since this compound is wasted in the urine.  Carnitine is required for muscles to break down fat into energy, and carnitine deficiency leads to accumulation of fat in muscle tissue.  Giving patients carnitine supplements will normalize blood and muscle levels of carnitine, and it reduces accumulation of fat in muscle tissue, but no studies have been done to assess whether carnitine replacement results in higher muscle mass or better growth in the long term.   Dr. Doris Trauner, a neurologist, mentioned in her remarks at the CRF conference that other proposed treatments for muscle wasting include coenzyme Q and the different B vitamins. 

Dr. Mak has been studying the effect of vitamin D on muscle wasting using a mouse model for cystinosis.  In the mouse model, the gene that codes for the cystinosin protein has been "knocked out," so the mouse no longer makes the protein.  This effectively creates a mouse with cystinosis, and it is a good surrogate for testing different therapies, like vitamin D. 



Normally we make vitamin D in our skin, with exposure to sunlight.  We can also get vitamin D from fortified foods, or from supplements.  If the supplement is from a plant, it's called ergocalciferol, or D2.  If it's from animals or our skin, it is called cholecalciferol, or D3.  Whether we make it in our skin or eat a supplement, the vitamin D is modified by the liver to make 25-Vitamin D.  This form of vitamin D is then modified again by the kidneys, to 1,25-Vitamin D, which is the active form.  This form is also called calcitriol, and it is required to maintain calcium and phosphate levels in the blood and promote bone growth and remodeling.  1,25-Vitamin D increases absorption of calcium and phosphate in the intestines, both of which are needed for bone mineralization.  Patients with renal failure often have to take calcitriol because their kidneys can't make the active form anymore.

Dr. Mak pointed out three reasons cystinosis patients have low vitamin D: they lose it in their urine, they spend less time outside in the sun because of photophobia, and they develop chronic kidney disease. Doctors have always known that it is important to treat vitamin D deficiency in cystinosis patients, since vitamin D deficiency leads to rickets (in addition to the phosphorous wasting seen in Fanconi syndrome).  Low vitamin D levels may also be bad for the muscles.

Dr. Mak has shown that cystinosis mice with vitamin D deficiency have smaller muscle fibers, weaker grip strength, poor balance, and energy wasting.  He has also shown that vitamin D deficiency leads to genes being turned on that break down protein, which leads to muscle wasting.  He treated cystinosis mice with 25-Vitamin D (the kind your liver makes) and 1,25-Vitamin D (the active form that your kidneys make).  He found that in the mice treated with 25-Vitamin D, there was restoration of muscle mass, muscle fiber size, grip strength and balance, more than in the mice treated with 1,25-Vitamin D.

Remember that 25-Vitamin D is just the regular over-the-counter supplement after it is modified by the liver.  This is the form that the muscle uses, because the muscle has its own enzyme to activate it.  So while 1,25 Vitamin D (calcitriol) is crucial for bone health, it does not appear to be as important for muscle health. 

So what is the take home message?  Vitamin D deficiency is bad for muscles, so taking a vitamin D supplement is a good idea if you have low levels, and it may even help prevent muscle wasting.  This doesn't mean you should just start taking big doses of vitamin D, however, because you can theoretically get vitamin D toxicity.  Dr. Mak and Dr. Grimm said that if your doctor hasn't done it already, get your vitamin D levels checked, and if you are deficient, then take a supplement.



We built Sam and Lars a rock climbing wall in their bedroom to help them with limb muscle strengthening, especially arms and hands.  We have absolutely no evidence that it will make a difference in the long run, but it seems like a good idea, and they have a lot of fun with it!