As of this month, I’ve had 13 years of unexplained issues with balance and falls; POTS; weakness; cognition and memory; fatigue; joint pain; skin problems; clumsiness and gait; tinnitus; and male fertility. I’ve had MRI’s, heart checks, endocrine workups, dietary changes, etc that don’t reveal significant abnormalities. The issues have worsened in recent years, to the point where I’m now largely bed-bound, with the exception of my full-time desk job.
Initially I maintained a pretty positive outlook that I would find and treat the issue, but in the last few years depression has definitely set in. A non-specific anxiety has also emerged, to the point where it’s hard to interact with people normally and mask the underlying sense of terror. It literally takes all I have to stay working, and that has begun to slip as memory problems have grown increasingly significant. It is also very difficult to sit upright for extended periods.
Last month I was prepared to ask my GP about long-term disability, as I’m beginning to feel the job is not sustainable. My doc’s diagnosis-by-default has been ME/CFS, which can make it difficult to qualify for state assistance here in the US. He suggested first doing another round of blood tests, so I kind of see this as my last-ditch effort to find something actionable.
For the first time, he mentioned the possibility of PA. Homocysteine has been high for years, and I’ve occasionally been slightly anemic, but B12 deficiency was initially ruled out a decade ago due to serum levels being in the normal range.
However, there are other indicators of a possible functional deficiency including very high folate and low iron saturation. FE itself is normal, but has previously been very high (?!).
The doc suspects methylation problems, a theory supported by my bad reaction to methylfolate supplementation, as well as a lack of reaction (positive or negative) to various medications.
I’m also checked annually for myeloma, as light-chain ratios are slightly off., but there are currently no other signs of that to explain the 13 years of symptoms.
The symptoms are most definitely a match for PA, but the problem is that methylmalonic acid (MMA) is normal despite all of the other flashing arrows.
My doctor doesn’t know what to make of these tests. He will likely refer me to a hematologist, but in my small town there aren’t many and that will likely take months to get in, with no guarantee that I’ll get more than another basic blood count and a prescription for this month’s preferred flavor of antidepressant.
My experience with specialists in my area has been that they will request basic blood work, but if the results don’t clearly point to something, they’ll say “OK, good. See you for next year’s check-up!” without further exploration. I don’t seem to be very good at communicating how disabling my symptoms have become. My GP isn’t particularly insightful, but I’ve stuck with him because he’s been the only one willing to go beyond the first level of testing to look for functional deficiencies, etc.
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In summary:
Symptoms: exact match for PA, even oddly specific things like cracking lips and proprioception problems.
Serum B12: normal range
Folate: very high
Homocysteine: very high
MMA: normal range
Iron level: presently normal , occasionally very high
Iron saturation %: low
IF antibodies: results pending
RBC: presently normal, occasionally slightly low
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I will likely try B12 injections anyway, as it’s fairly easy to self-treat in the US, and there’s some indication they can help with fatigue even when a deficiency is not present. However, my hopes for B12 being a major game-changer have diminished with the normal MMA result, as that’s typically the gold-standard marker for a functional deficiency.
Since PA patients in this forum seem to be very knowledgeable on blood work, I would be interested to know if anyone has any suggestions for follow-up testing that might help unravel this mystery. My GP and I are both out of ideas.
Thanks.
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Woozy1
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Recent paper extract : "MMA concentrations are elevated in only 56% of people with serum B12 concentrations < 140 pmol/l, and in 13.5% of people with serum B12 in the grey zone of 140-300 pmol/l." njmonline.nl/article_ft.php...
It sounds to me like you may best off to trial B12 injections for a time (you can probably get them done at a local beauty salon or equivalent for not much cost) and see if your symptoms respond. The first injection is best done under medical supervision in case of rare severe reaction such as anaphylaxis. Consider also other elements of your methylation ingredients such as B2 and particularly B6. Do you have regular B12 sources in your diet?
Thanks for the response. Yes, I’m a meat eater with a pretty decent diet, very light on processed foods and sugars. Serum B12 was 450, so doc and I had hoped Hcy/MMA levels might indicate a functional deficiency to explain symptoms. Hcy and folate are elevated but MMA is not. Doc’s office did an initial B12 injection with cyanocobalamin, with no reaction either way. If I self-treat, I’m thinking methylcobalamin due to suspected methylation issues. Might request gene test for MTH, but not sure that would offer any guidance for treatment, given the seemingly contradictory bloodwork.
Regarding B2/B6, I will definitely look into those. I’ve at times supplemented a good B-complex orally, but it didn’t change symptoms.
Hm. An interesting case for sure. I suspect some methylation problem - no response at all to the B12 injections is curious, so sounds like other factors are in play.
Thanks, Nackapan. BP tends to run slightly high at rest, but drops quickly when rising, and heart rate remains elevated to compensate (POTS) when seated or standing. I've worn a 24-hour heart monitor that revealed some mitral valve prolapse, but according to the cardio, not enough to explain the symptoms.
I also had a fairly thorough thyroid workup a few years ago, covering even uncommon tests like reverse T3. All appeared normal.
Ferritin is occasionally high and iron saturation % is low-normal, possibly suggesting an absorption issue. So far my doc hasn't felt these were worth pursuing as a primary cause of symptoms, rather just more clues to the mystery.
If you have a long standing B12 deficit one injection is just a drop in the ocean. I think doctors think that B12 is a drug and expect instant results.
Agreed - neither I or my doc expected results from that first injection. I only mentioned it because Technoid had mentioned the danger of anaphylactic shock on the first one.
How awful to hear you have suffered all these years without finding a cause. I would definitely request a loading dose of B12 and carry on with injections even if you have to do them yourself.
Drs seem to think a MMA test rules a B12 deficiency out - it does not. There ignorance is not acceptable when patients are suffering such severe life changing debilitating symptoms. I was unable to function throughout my day and albeit my Dr gave me the loading dose and 3 monthly injections my symptoms were not improving.
It was only when I took matter's into my own hands and decided to self inject I slooooowly started to recover. Some symptoms were worse before better especialy the stinging and burning in my legs but that has also now improved. It's taken a couple of years to improve my gait, balance, mood ect but I am regaining 'my life' little by little.
Sometimes I have a slight set back if something else is going on such as a chill but at those times I simply inject more frequently. At present I inject daily which is a bit of a pain but I am now in control.
This diagnostic flowchart from a UK B12 document suggests that doctors should consider continuing treatment for B12 deficiency in patients who have responded (symptoms improved) to b12 treatment, even if MMA/homocysteine and Active B12 (holotranscobalamin) tests are normal range.
Have you had an Active B12 (holotranscobalamin/holoTC) test?
The results of this test are likely to be affected if you've had B12 injections/supplements.
You have raised homocysteine and symptoms consistent with B12 deficiency. To my mind, (I'm not medically trained) these both suggest B12 deficiency is a possibility.
In UK, NICE (National Institute of Health and Care Excellence) guidance B12 deficiency and BSH Cobalamin and Folate guidelines suggest that people who are symptomatic for B12 deficiency should be treated even if serum (total) B12 is within normal range. It can sometimes be a real fight in UK to get NHS doctors to do this.
You mention having one B12 injection which I suspect won't make a lot of difference especially if you've been ill for a long time.
My B12 deficiency was not recognised for many years. It took weeks or even months of every other day B12 injections to start to see improvement.
Although I had one previous b12 result that was well below range, all my other serum (total) B12 results were within normal range and I deteriorated to the point of dementia symptoms and symptoms affecting the spine.
Your doctors might find this PubMed case report interesting which mentions functional B12 deficiency.
"What You Need to Know About Pernicious Anaemia and B12 Deficiency" by Martyn Hooper
Martyn Hooper founded PAS (Pernicious Anaemia Society).
"Could it Be B12?: An Epidemic of Misdiagnoses" by Sally Pacholok and JJ. Stuart (US authors)
Very comprehensive with lots of case studies.
Sally Pacholok has written several online articles about B12 deficiency which may be worth searching for. I also found a presentation online she made to a conference in US.
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