Our 8 year old has had an uptick in symptoms

I'm looking for suggestions on how to help our youngest daughter who is now 8 and suffering from crushing fatigue. Our teen daughter and I didn't have the fatigue this bad at her young age. Any suggestions would be appreciated.

In the last few months, she has missed a lot of school, stopped going over to most friends houses, and on days when she had activities including dance, church choir, and lacrosse - she no longer looks forward to going because she is so brutally exhausted and therefore has not been going.

The school is fully aware and supportive of her time off for MitoD. Her recent blood test came back with the following issues:

White blood cell count - Low - 4.2 (4.5-13.5)
Red blood cell count - Low - 3.93 (4.0-5.2)
Hematocrit - Low - 33.9% (35.0-45.0%)
Absolute Neutrophils - Low - 1281 cells/uL (1500-1800)
Alkaline Phosphate - Low - 144 (184-415)
Vitamin B12 - High 1581 (250-1205)
Vitamin D - Low 27 (30-100)

In the last few months she has had a few bouts with illness (high fevers), but nothing unusual with this crazy flu season. Her eczema on her top lip keeps popping up (red crusty looking infected for a half inch above her top lip). Usually, a little cream helps this go away and stay away for months. Her toe the other day had an infection out of nowhere. Maybe these are due to her low absolute neutrophils.

It's odd that her B12 is high when we do not supplement this and she tries to avoid meat at all cost and therefore eats only what we require. She would love for us to allow her to be a vegetarian (and she will likely go that direction when she is older). Her MitoD doctor sent a note that she often sees high B12 in MitoD kids stating that she "has frequently observed high B12 levels in other patients who are not on supplements either." But she didn't elaborate why.

We have started increasing her D3 supplements to 2000 per day (per the doctor).

Weak teeth and mineral issues is a big concern for all of us. This daughter will be going in for a root canal on her 6 year old molar and a tooth extraction in a month in the hospital. Due to tooth weakness, it works out best to be done in hospital. For example, during a tooth pull over a year ago, the tooth pull broke in her gum. They sent us to the Children's Hospital Emergency Room. They had to do emergency surgery right there due to complications. They want to avoid that from now on. While they take care of this most recent tooth issue, the Mito surgeon is also going to do a muscle biopsy at the same time.

If there is anything you can think of which we have missed to help her with energy, please let me know. I hate to see our precious 8 year old so exhausted all the time. Usually we don't see this uptick in severe fatigue symptoms until around puberty in our family.

Thanks!

 

Iw sorry @BeautifulDay , I have no idea or suggestion. Just to you both. I hope you find some answers.

 

Has her folate levels been tested? Eating a lot of vegetables would usually mean that folate levels are doing great, but "mostly vegetarian" doesn't always mean lots of vegetables, as my own little cousin nicely demonstrated

Dance and lacrosse might simply not be feasible, and the lacrosse might be especially difficult due to the pressure to keep up with teammates and not feel like she's letting them down. Dance also seems to be incredibly demanding of energy, at least from what I've seen watching Dance Moms (don't judge me ).

Could choir be a problem due to standing still a lot? That can be an issue if she has low blood pressure or pulse pressure, which can be hard to notice if it's a slow onset of symptoms which only hit after being upright for a long time, such an neurally mediated hypotension which often takes 30+ minutes to hit. If so, sitting for choir could make a big difference.

But maybe she could switch to lower impact activities that still have her interacting a lot with other kids, which also provide a safe level of activity which might be beneficial in genetic mitochondrial diseases. Band was a lot of fun for me (I skipped out on the marching in high school though), and there's things like art classes as well. And if she is an enthusiastic veggie-muncher, gardening might be a lot of fun for her as well.

It also might help to figure out the proximate cause of exhaustion: blood pressure, oxygenation, heart rate, and lactate levels can all be measured with devices at home (or at the field, or the dance studio). Orthostatic intolerance is often treatable and can even be transitory, though I'm not sure how much that applies to mitochondrial diseases specifically.

 

What is her ferritin sitting at?

 

Has your daughter had an iron panel done or thorough tests to check for anaemia? With low red blood cell count and low haematocrit it would be worth doing.

On the subject of high vitamin B12, this might be of interest, although it is also likely to be very worrying in places, sorry :

Link : https://academic.oup.com/qjmed/article/106/6/505/1538806

Title : The pathophysiology of elevated vitamin B12 in clinical practice

 

Thank you @Valentijn . Her folate was recently tested at the same time and was listed as normal at 22.0 ng/ml with the range being >7.1.
You are correct, she doesn't like meat or vegetables or anything with flavor .....

I hadn't thought of an art class instead. She would absolutely love that. Two weeks ago when she made her lacrosse practice, they did a very light run and it was the first time she was having a breathing issue and she said her heart felt like it was jumping out of her chest unlike anything she had felt before. With my exercise induced asthma and POTS in my teens, I understand that feeling. I just didn't expect it in her (or at this young age). She had to give up her beloved gymnastics last year because it became too dangerous with her foot drop that comes and goes and the gymnastic landings.

In class, her teacher said she never puts her head down like other children. Her teacher can read her face and pale white coloring to how she feels, but she'll be stoic before putting her head down. Then she gets in my car and has a meltdown everyday on the way home after school from trying to pretend she has normal energy and suffering through the day. We may have to get her an IEP soon for shorter days. I hope not though. I've offered to bring her home for lunch and recess for an hour of rest everyday, but she doesn't want to lose time with her friends.

Sitting down at choir. I'll talk with her about this. Thanks for the idea!

Our Children's Hospital won't do the exercise testing (looking for oxygen uptake and quick turnover from aerobic to anaerobic) until she reaches 135 cm (53 inches). We've got 5 inches to go. She's seen the cardiologist and all is well with her heart.

The doctor's don't seem to have a clue how to treat our orthostatic intolerance issues in the rest of us in the family, so I don't hold out hope that they'll have a treatment for her. Pretty much they figure out through various tests we have this or that and then are told they don't know how to treat it in us because of other issues or the severity that comes and goes. I'd love to hear how others are having their orthostatic intolerance treated.

I watched Dance Moms for the first season. Too much drama for me. I veer away from drama in my life, so watching it on TV is too much for me. I tend towards the crime investigation series that fall more into Cozy Mysteries. Monk, Columbo, Murder She Wrote, Mrs Marple, Finder, Death in Paradise.

 

Great question! I just went back to her last blood test. She wasn't tested for ferritin. I then went back through all her labs for the last year from the hospital and it doesn't look like anybody tested for ferritin.

On Monday, I'm going to ask for a lab slip for this. We can then hold onto it for when she gets her pre-hospital visit testing (in one stick).

Thanks!

 

Thanks Arnie! Great information. I don't tend to worry about things. I take in information, evaluate and then try to figure out the course. Knowledge is power. I ask questions, I ask about possible tests, and bring in medical journal articles to discuss at appointments. I am not the patient (or patient's mother) for doctors who don't like in-depth discussions with their patients.

With our family having a history of aminoaciduria and high proteins in urine (and some in blood), the B12 issue with protein and possible kidney issue is worth fleshing out. Thanks for the insight.

 

@BeautifulDay . . . regarding ferritin levels, make sure you ask for the the actual test results because sometimes doctors will tell you 'it's fine' based on reference range. I'm not sure what the ideal level is for an 8 yr old, but I know upper 40-60 is recommended for adults.

When my ferritin levels got below 20 I was unable to walk for very long and felt dizziness.

 

Thanks @Mij . Will do

 

Interesting that a MitoD doctor has noted that. There were a few of us (myself included) back on the other forums that talked about finding B12 testing similarly out of range without supplementation. I think we'd probably know about it by now if it were caused by one of the really serious causes noted in that paper posted. I pushed for MMA and homocysteine testing to explore further but the NHS lab bounced it back because, duh, you have plenty of B12.... sigh.

I have follow up with a muscle disease clinic next week for Acylcarnitine Profile results (investigating fatty acid oxidation and organic acid disorders), i'll see if my doc has heard of anything similar with B12 status.

Ryan

 

I wonder if vitamin K2 (MK4) would make any difference in her symptoms, since its not ME/CFS. It would help the teeth/bone strength if combined with Vitamin A/D, but it will push on wisdom teeth if they are present.

 

Just ferritin on its own isn't sufficient to tell whether your daughter has too little or too much or just the right amount of iron. You would need a full iron panel done to be sure whether or not it would be safe or possible to supplement.

These are the tests which are needed : http://www.healthcheckusa.com/hemochromatosis-iron-tests/iron-panel.aspx

And you may find this link of some interest : http://www.irondisorders.org/Websites/idi/files/Content/854256/HowdoIknow_Anemia__Converted_.pdf

 

Thank you @Alvin . I'll ask her doctor about it. Since I passed Factor V Leiden heterozygous onto this little one, her doctor might frown on Vitamin K2 due to increased clotting risk.

 

I'd be surprised if the doctor will know much about it, but clotting risk is not an issue, it works very differently from K1. Its something you should look into before you see the doc because the default advice will be don't try it, the idea being its hard to go wrong by playing it safe but if it will help you will never know by not trying it.

 

Thanks @Alvin . I completely understand. I'll do the research on K2. I really appreciate the heads up.

 

Your welcome, let me know if you have any questions, i researched the hell out of it a few years back. Also MK4 works better then MK7 for most things, the only advantage to MK7 is it needs lower doses to active osteocalcin probably because the body does not use it as much elsewhere.

 

I pushed for the blood tests mentioned. Here are her results.

Ferritin was normal (middle of the range).
Iron normal (but higher end of range).
Transferrin normal (but lower end of range).
TIBC normal (but lower end of range).
Transferrin Saturation HIGH (43% with range of 6-40%).

When I was at my worst a few years ago memory wise (severe young onset memory issues), they found the following:
Ferritin (low at 14 with range of 25 - 160)
Transferrin Saturation (high at 50% with range of 20 - 45%)

I was told it was unusual at the time to have low ferritin and high transferrin saturation. Transferrin saturation going up into high zone is usually the first sign of iron overload. That could explain the feeling toxicity every day (as if hung over every day). Of course amino acidurina, etc... also adds to that. Being on the low end of ferritin can make the fatigue that much more difficult.

When on low iron pills I got toxic and started slurring my words and feeling like I was being poisoned. I lost the ability to speak in sentences, had headaches non-stop, foot drop was constant etc... Going off the iron pills stopped that and made my normal low fatigue and crazy intermittent symptoms the norm again. Then when I got the copper IUD, same thing. Very toxic.

It was explained to me that I was one of those odd people who get toxic on iron and copper, yet it doesn't get into all cells well enough to provide what is needed. Complex. So I was left on my own and tried my best to level it. My middle ground right now is little chicken and lots of spinach. It doesn't make me as toxic, but provides the best energy level I can get right now.

But to see our 8 year old with high Transferrin saturation at this young age. I believe it's time to revisit this with the docs. Maybe over the last few years, they'll have a better answer for us now.

Any body with a similar issue? Any body have any suggestions? I will tweak anything to try to get us as close to normal. Doctors would never spend the time doing this, but without it we'd be so much worse.

 

1) Does this link help? https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/transferrin-saturation

2) Did your daughter have her blood taken first thing in the morning, having fasted for 12 hours?

3) Has she been on iron supplements at all? And, if yes, did she stop them for a week before testing?

4) If you are worried about hemochromatosis then this page may be useful : http://www.americanhs.org/faq.htm

5) I wonder at what age people can start to show up signs of iron overload in blood tests? It might be worth finding out.

I can't offer any definite help - I have no medical training.

 

Thank you @Arnie Pye . I appreciate all efforts at getting to the bottom of this.

I had come across the web sites you mentioned. Both are interesting.

2. For the blood test, she was not fasting and it was in the morning (but not first thing in the morning). I read a lot of articles that mention using fasting for the various iron serum tests, but I couldn't find any of them backed up studies. However, I did find studies that stated it did not matter if with fasting or the time of day. If you came across a study for fasting or early morning testing, I'll put it in front of our doc.
Study stating fasting vs non-fasting not matter,
"However, this study and other previous studies have failed to confirm the added value of fasting iron tests compared to random iron tests (18, 22) and variability in this study was similar between homozygotes and non-homozygotes. Fasting adds a level of complexity and inconvenience to a screening program. As illustrated in this study, the second fasting value is as likely to increase as decrease and regression to the mean is the most likely explanation."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151312/

In this study, they concluded that:
".... the practice of restricting iron specimen
collections to a specific time of day does not improve
the reliability of the test result."
https://watermark.silverchair.com/a...VbMgqDBBYWDLr7GzM68N5f6VtE9C0MmchkIdOjebkNHWP

3) She was not on iron supplements. She never has been. Also she hasn't eaten red beef in years. It tastes metalic and gross to her. It's hard enough to get her to eat chicken and ham.

5) From the studies I have read, iron overload can show up in childhood. Usually the first symptom is the elevated tranferrin saturation like our daughter has.
http://www.irondisorders.org/juvenile-hemochromatosis1


Many iron test websites have charts similar to this one from the Iron Disorders Institute.
http://www.irondisorders.org/tests-to-determine-iron-levels/



Our daughter really doesn't fall under any of these. We were first looking at possible anemia or low iron because of her low hematocrit and low white blood tests. They weren't crazy low. But with her feeling so fatigued, anything we could do to increase her energy is worth it. So we pursued the iron tests.
With low hematocrit and high transferrin saturation, there are a few up there for these two test results. However, Sieroblastic Anemia and Thalassemia and African Siderosis and Vitamin B12 deficiency don't fit.

Actually thinking out loud, maybe the B12 deficiency does fit. She is high B12 without supplementing. Yet, she eats little meat. The Mito doctors said she has seen this happen (high B12 without supplements) in many MitoD patients. There are people who have trouble absorbing B12 into the cells and are deficient, yet it can be high in their blood. I don't remember where I read that. I'll go back and search. Therefore they look like they are high and not deficient of B12 on blood tests, but are actually starving for B12.