Thursday, September 6, 2012

John's 1st day of 4-year old preschool

I think this year John is going to do great in preschool. I'm really excited about his preschool teachers and all the fun things they have planned for him to learn!

I want to capure some of what John is doing and not doing at the beginning of this year, so that hopefully at the end of the school year I can look back to see the progress he has made.

This summer he has started saying the alphabet. He gets to letter H and then skips to W, X, Y, Z  but he is slowly starting to fill in the missing letters. He can count to 14. He knows how to spell "Stop" and "John." He can follow 3 step directions. He can put his flip flops on with a strap in the back, but I think we will need to work on tennis shoes this winter. He can pull up pants with elastic waist and is starting to learn how to put his shirt on. He can brush his teeth. His sentences are so long that I don't even know how many words are in them now! He can cut paper in straight lines.

A few things I hope he'll learn - how to use "He & She" right now he always says him & her. Use more words like "to"  Right now he says, I like play ball. Maybe by the end of the year he'll say "I like to play ball." How to sing a song like "happy birthday." He doesn't push on crayons very hard and has a hard time coloring, so I hope he'll get better at coloring this year.

I can't believe I am sitting here writting out these goals of my hopes and wishes and dreams for him for this year. Not because it's bad to have those for your children, but because I can't believe how far he has already come and how many goals he has already reached and surpassed!

Sunday, July 8, 2012

Interesting Lab Results - Learning more about GAMT

This is a conversation that took place on our facebook support group.

And the Results are in...

Gave John his last supplements around 6pm.
Went to Duke and had 1st Blood Draw at 9am (15 hrs later) - no supplements that morning, no food.
Feed John a 4 oz yogurt with 3 grams protein along with his milk & all medicines apx. 9:45am
Repeated Blood Draw 4 hours later

1st Blood Draw....
7.1 GAA
40 Ornithine
124 Creatine
40 Arginine
201 Glycine

2nd Blood Draw... (4 hours after 1st)
5.2 GAA
241 Ornithine
352 Creatine
50 Arginine
195 Glycine

A few comments. I was surprised at how much the GAA level moved. I was not expecting this. I had thought up until now that the GAA level moved more gradually over time.

Another surprise... I would have thought the Arginine level would have increased more than it did. I gave him a 3 gram protein yogurt and it didn't make that much of a difference in the arginine level. I had wanted to feed him one of the highest foods with protein in it to see what would happen. My guess is that it didn't increase much because of the ornithine counterbalancing it, but makes me wonder, what if it would have been a bigger thing of yogurt with 5 grams of protein? Would the GAA level and arginine level have been the same? I gave John a 3 gram yogurt, yet his GAA still went down and the arginine only went up slightly. Makes me wonder, can John be eating more protein than I'm giving him?

Also, makes me realize that I should try to give him his nighttime dose of medicine as close to bedtime as possible to keep everything from dropping off overnight and therefore preventing the GAA level from going up.

Let me know your thoughts. Dr. Clark - What do you think about these results?

Joseph Clark Missy, thanks for this. I’m going to need to assume the GAA concentration is in micromolar and normal should be about 1.2. Is this what your lab is saying? GAA is found in very few foods and none of the foods I saw listed. So the body (Kidney and Liver mostly) is making GAA and ornithine via AGAT most all of the time and a lot of that is done at night. When you gave John the creatine and ornithine at 9:45 AM, the signal to make GAA was inhibited by the ornithine and creatine. Yes, that is kind of a quick fall, but also the body prioritizes what it spends time doing. When we eat the body gets flooded with stuff to do as far as managing toxins in the food, hanging on to good things in the food etc. Hence, a large percentage change in GAA for a short period of time could occur. I’m not sure of the sensitivity in the kidney for excreting GAA. One paper I found said it was about 5 micromolar. Which means that once the kidney stopped making it the kidneys were excreting it. So I think the GAA fell so much because of the excretion into the urine and the decreased synthesis. Were urine levels done?

Arginine and glycine are amino acids used in many other processes and in many foods. I have to admit I am not convinced that very strict protein restriction is necessary in GAMT patients especially in growing children. I know it is hard for parents to know what to do because the experts do not agree. We don’t agree because we really do not know. So I for one very much agree with you suggestion that John could be eating more protein. What the right level is or the best proteins, we still do not know. Ornithine would not be a reason for the arginine not increasing as much. Ornithine decreases the amount of arginine consumed by AGAT.

I very much agree that giving night time meds/supplements as close to bedtime for the reasons you suggested. The body’s chemistry goes into overdrive at night, so this strategy might very well help control things.

My general impression of the results is they have a lot of good news. I think it is great that the GAA does change and that John’s body is responding in a positive and controlled way. Positive that GAA goes down, controlled that arginine and glycine do not change much. I also think that it indicates that at this time John’s body is ready to handle the proteins and amino acids in his diet. I say “at this time,” because as we get older and as John stops growing the ability to handle the arginine and glycine may change.

What none of us really knows is what the right level of GAA is; referencing the 5.2. Labs report different numbers as normal and use different units. We think we know what average is in people with normal GAMT and AGAT activity. But we do not know what GAA should be in GAMT patients. We know that GAA can inhibit creatine kinase in the brain and eventually lead to seizures and other bad things in the brain. So it is something we must pay attention to, but with relatively little hard data to go on.

Best wishes.

Post from another GAMT mother: This makes me feel like spreading creatine and ornithine into more than three doses would be helpful. Maybe first thing in the morning, lunch, afternoon, and evening? At one point my nutritionist said that food and supplements should be in proportion, meaning give half of her day's supplements if there's a meal where she eats half of her day's allotment of protein. Dr. Clark- are you feeling like that is completely inaccurate and that the body is making GAA anytime, food intake or not, based on John's results? I had heard "the supplements work with her food" as if a dose late in the evening on a near empty stomach would be a waste? What do you think?

Joseph Clark  I think there are a couple of things to consider. 1) most of these supplements do work on an empty stomach. BUT and importantly 2) they are somewhat like salts. So if taken on an empty stomach they can, in some people, cause an upset stomach. I’ve done this to myself with creatine (with and without food) and taken with food feels better. With regard to in proportion for creatine and ornithine; that is not necessary. The most important thing is to make sure Sam gets what she is prescribed each day. I do believe that the body is making GAA nearly all the time (outside of starvation or disease). It will increase and decrease though based on modulators such as ornithine and creatine. I do not think a dose on an empty stomach would be a waste metabolically. But do make sure she does not get an upset stomach.
To explain my concern regarding the upset stomach. Creatine in the stomach acts a lot like a salt. If you eat a bunch of salt it can cause water to enter the stomach and make a person feel nauseas and even vomit. We want to avoid that with Sam and the other GAMT kids because it would make giving them the creatine and treatments harder.
Regarding your nutritionists, he/she is correct with regard to pure “dietary supplements” as a dietary supplement is often something that helps the body absorb or metabolize something else. But for Sam and children with GAMT creatine and ornithine are much more than dietary supplements and more like drugs that the body needs to have a fairly constant supply of as part of the treatment. Creatine is supplying the body with creatine for energy metabolism AND inhibiting AGAT. Ornithine is inhibiting AGAT so less GAA is made.

Finally, when we get back to the protein restriction. That is theoretically done to decrease Arginine and glycine, which are the molecules used by AGAT to make GAA and ornithing. My personal opinion is that it would be very hard to restrict arginine and glycine to low enough levels where AGAT would be unable to use them to work. Remember the body needs them for other things. When I did the rough math calculation, excuse the science and math here, I estimated that the arginine would need to be 2 (John’s was 40 after fasting) and glycine 3 (John’s was 201 after fasting). Again, no hard scientific evidence but I am still not convinced that protein restriction is absolutely necessary because it is impracticable to get low enough to be effective. However, don’t change what your physician recommends without consulting him/her.

Missy- thank you so much for sharing. I think this is a step in the right direction- and knowing how the levels adjust in such a relativley short amount of time. wow! I wonder what would happen if we gave the largest dose of creatine/ornithine in the evening? I'm intersted to see how the sodium benzoyte might change these #'s too?

Dr. Clark, Thank you so much for your input. Your contribution is so appreciated!

§        Dr. Clark's response - Sodium benzoate works by pulling ammonia out of the body. Ammonia is converted to urea for excretion in the urine by going through the urea cycle. The urea cycle starts when ammonia is converted to carbamyl phosphate. Carbamyl phosphate commits the body to making urea. The VERY next reaction consumes ornithine. So when sodium benzoate is given to the GAMT patients the thinking is it is sparing the loss of ornithine by the urea cycle. If ornithine is not consumed by the urea cycle maybe it can stay around to inhibit AGAT. That is the theory. Sodium Benzoate has a long history for treating patients with urea cycle deficits and is generally considered to be safe. It is actually found in some foods as a preservative. Based on its safety and the importance of sparing ornithine I do think the sodium benzoate is a good option for GAMT patients. I think some physicians may be hesitant to use it in GAMT patients because usually sodium benzoate is indicated to decrease ammonia, and may feel uncomfortable prescribing it when someone has normal ammonia. Hopefully if there is a concern it can be addressed. One caveat for anyone talking to their physician about management of GAMT. I am not comfortable with a treatment that would have strict protein restriction and sodium benzoate simultaneously. The reason is this will change the body’s nitrogen metabolism in ways we do not understand. In a growing child their body needs ammonia and nitrogen to grow. So combining very low protein and sodium benzoate should be avoided. I’m sorry this is getting so complicated, but I think it is important. We want the children with GAMT to continue to grow and develop normally and changing protein and ammonia metabolism too much will impact on normal development.

Sunday, August 21, 2011

Dr. Joseph Clark Announcement- Cincinnati Children's Hospital

The following is from Dr. Joseph Clark of Cincinnati:

As I hope many of you know I am dedicated to the study, diagnosis and treatment of the creatine transporter deficiency disorders called: GAMT, AGAT and CTD. I have blogged on these subjects several times before and have an announcement. Here in Cincinnati we (University of Cincinnati and Cincinnati Children’s Hospital Medical Center*) are launching the first of its kind diagnostic for all three diseases. Previously patients often had to have multiple doctor’s visits and can take many months to get a diagnosis. Now, gone are the hassles of sending samples to three different labs, that were collected in different ways at different times. One visit, one collection method and one lab can do the genetic diagnosis. The launch of this new service is August 1 2011. More info about this service can be found here:

This one stop shop concept for the diagnosis of the creatine deficiency syndromes will save time and angst for the doctor, patient and caregiver and is especially important as these diseases, when treatable, require early treatment to achieve optimal benefits. There are many anecdotal stories of families who have identified a deficit with their child at an early age but take years for a diagnosis. The late diagnosis often leads delay in treatment and can result in prolonged deficits in the patients. Time is brain for many of these patients and our new system will save time.

We are happy about the launch of our new diagnostic technology. Please spread the word to patients, doctors and advocates so that we can diagnose these patients early and effectively. Check out our facebook group!/groups/127389967322193/ for future updates and more discussions on the creatine deficiency syndromes. Watch this space as well to see what we will be rolling out as we continue to work to help caregivers and patients with creatine deficiency syndromes.

Questions about the test can be sent here:, Questions about creatine deficiency syndrome research in Cincinnati can be sent to

*Please note, I am not a representative of the University of Cincinnati and/or Cincinnati Children’s Hospital Medical Center, but want to make everyone aware of what these outstanding institutions are doing.

John's Progress - 3 years old

John says approximately 50-75 words now. He can put two words together pretty good now “Mom watch” “Dad ball” “Mom come” and recently I’ve heard him put 3/4 words together…… he says oonnne, twoooo, eeee, go!

His speech therapist tested him back on March 3rd and he has made tremendous progress since this report. Back in March (2years 9 months old) He received a receptive language standard score of 104 and standard scores of 85-115 indicate age appropriate skills. And his age equivalence score put him at 2 years 11 months and he was only 2 years 9 months old at the time, so he actually scored above his age for receptive language skills. I think this has to do with the fact that he couldn’t talk very well, so the poor kid became a very good listener!  Receptively John was able to complete the following tasks: 1. Identify colors, 2. Make inferences. 3. Understand expanded sentences (“Point to the white kitten that is sleeping”) John received an expressive language standard score of 70 and age equivalence of 0 years 6 months. Expressively, John was able to complete the following tasks: 1. Imitate words (ball), 2. Use 5 to 10 words 3. Use vocalizations and gestures to request toys or food. John was Unable to 1. Produce different types of consonant-vowel combinations, 2. Name objects in photographs 3. Ask questions.

John’s gross motor skills are excellent! He runs, jumps, does the monkey bars with just a little support, can climb up a slide, jumps from 3 feet in the air and lands on his feet, climbs a rope ladder, walks a balance beam, his balance is excellent, he can kick a ball, throw a ball, he can even sometimes hit a ball with a bat when you throw a ball to him, but he is probably only hits about 2 out of 10 pitches, but I’m sure that for his age that is probably excellent. I’ve even had some parents think that he is 4-5 years old when they see him playing on the playground and I think part of that is that he has no fear and he is so light that I think he just moves very easily.

His fine motor skills are ok. He has good movement in his hands, but it is just a matter of strength and not dexterity. He has a hard time pinching off a piece of play dough or pressing really hard on it. It is hard work for him. He is just now learning how to pull off one of his socks and it is hard for him. He struggles pulling up or down on his pants and I think that is because he can’t get a good pinch on them. He has just recently learned how to take off his shoes, but he is a long ways off from learning to put them on and I think that is something he should know how to do by now. He can’t do buttons.

Saturday, April 9, 2011

John's original MRI results

I just thought this might be interesting to post. I often have mother's of undiagnosed children that contact me when they stumble upon information on my blog. I thought I might post this in case anyone searches for a similar MRI result. John's original MRI from when he was a year old showed evidence that he had some damage in his brain. The report read: There is abnormal T2 signal hyperintensity in the globus pallidus bilaterally. There may be slightly restricted diffusion in association with this abnormality. The rest of the report just goes into detail that everything else is normal.

Tuesday, March 8, 2011

John's Words

I was asked recently to make a list of all the words John is now able to say. He has made some great progress recently. Most of these words he still does not say the way we would say them and some are probably only understood by us, but here is his list and a simi interpretation of the sound.

Bye - bye
Hi - ayyee
up - paah
off - aawwf
on - aann
Bubbles - buh buh
pop - paahh
hot - haaah
yes or yeah - aah
Emma (the dog) - EEEEhh (in a loud voice, just like we call to her)
dad - AAAAhhhhd (he yells for him too)
blue - boo
purple - puh puh
Green - eeenn
Please - ease
Help - eeellp (yelling again)


We found out recently that John has an iron deficiency, so he is now on an iron supplement. That means 4 supplements now, three times a day!