Thalassemia or the possibility of an acquired form

[SWAlexander]

Hello everyone,

Some days, I really wish my brain would just take a break!

I’m curious—has anyone here ever been tested for thalassemia, particularly when dealing with smaller-than-normal red blood cells?
I’ve included a few links below for those who have the energy and interest to dive deeper.

My most recent blood test once again showed red blood cells on the smaller side. Interestingly, I received similar results about 37 years ago, but at that time, no explanation or treatment was offered.

Back then, my muscle weakness had already progressed (I have had it since childhood) to the point where I had to stop working as a hotel manager—a physically demanding role that involved long hours on my feet.

In 2010, DNA testing ruled out inherited thalassemia but raised the possibility of an acquired form. For those unfamiliar, acquired thalassemia is rare and mimics the symptoms of inherited thalassemia, but is caused by other illnesses or conditions rather than gene mutations.

In 2016, UNMH suggested a diagnosis of myalgia. In 2020, neurology in Germany focused strictly on Myasthenia Gravis. Then, in 2022, I was diagnosed in the UK with Post-Polio Syndrome, among many other diagnoses such as Chiari Malformation I.

Most recently, in 2024, Prof. Spuler invited me for testing for dysferlinopathy, as not only my legs, but also other skeletal muscles are now affected.

And just last month, another blood test confirmed small red blood cells again. So now I’m asking myself:

"Could smaller red blood cells be a missing link in ME/CFS, fatigue, and thalassemia?"

If anyone has insights or similar experiences, I’d love to hear your thoughts.

Warmly, SWA

 

[Zebra]

Hi, @SWAlexander

Would you mind reminding me what tests reveal small red blood cells?

I recall having a few abnormal tests related to RBCs, but I am having a hard time recalling what type of test this would show up on.

Routine CBC with differential?

Peripheral blood smear?

Bone marrow biopsy?

Please let us know, thanks!

 

[SWAlexander]

tests reveal small red blood cells?

Thanks for asking.
Blood Test: Mean Cell Volume (MCV)

Example Result: MCV – 83 fL (my last lab results).
Reference Range: 83–103 fL
This result is at the lower end of the normal range, suggesting that red blood cells are slightly smaller than average but still within normal limits.
Every number below 83 fL is significantly below the normal range.

Note: A low MCV can be influenced by various factors, including iron deficiency or chronic physical exhaustion.

Hematology: One other contributing factor may be low ferritin levels, which indicate depleted iron stores.
Further evaluation is recommended to identify the underlying cause.

DNA: To detect genetic mutations in the HBB gene (for beta-thalassemia) or HBA1/HBA2 genes (for alpha-thalassemia).

Attention: High ferritin doesn't always mean iron overload, so it's important to interpret it in context with other tests like:

Serum iron
Transferrin saturation
Liver MRI (Ferriscan) – to directly assess iron levels in organs

Blood Test Results Interpretation​

1. Mean Cell Hemoglobin Concentration (MCHC):
Result: 35.2 g/dL
Reference Range: 32.0 – 36.0 g/dL
Interpretation: Normal
The MCHC indicates the average concentration of hemoglobin in red blood cells. A value of 35.2 g/dL is within the normal range, suggesting normal hemoglobin content per cell.

2. Platelet Count:
Result: 235 ×10³/µL
Reference Range: 150 – 400 ×10³/µL
Interpretation: Normal
This platelet count is well within the normal range, indicating healthy clotting function and no signs of thrombocytopenia (low platelets) or thrombocytosis (high platelets).

 

[Wishful]

I have thalassemia. Inherited I assume.

Is there a similar condition in which people have oversized blood cells? If so, are PWME who have that more severe? Do people with that have ME-like symptoms? Just a thought.

 

[SWAlexander]

Do people with that have ME-like symptoms? Just a thought.

Hi, I'm sorry to hear that you might have thalassemia. If you'd like to be certain, consider asking for a DNA test to confirm it.

 

[Wishful]

Hi, I'm sorry to hear that you might have thalassemia.

Why? It should have no significant effect on my life. It can't reduce my chance of getting malaria, since that's already effectively zero here in Alberta.

Hmmm, I should have said "thalassemia trait", since there's another more severe form that I think is usually fatal. I just have cells with 3 hemoglobins rather than 4 (or something like that).

 

[SWAlexander]

I just have cells with 3 hemoglobins rather than 4 (or something like that).

Do I misunderstand you?
Do you mean 3 copies in Gene?
Thalassemia does not cause red blood cells to have 3 hemoglobin molecules instead of 4.

Alpha-thalassemia​

Four genes are involved in making the alpha hemoglobin chain. You get two from each of your parents. The seriousness of alpha-thalassemia depends on how many copies of the genes are missing:

If one copy of the gene is missing, you'll have no symptoms of thalassemia. But you carry the disease and can pass it on to your children.
If two copies of the genes are missing, your thalassemia symptoms likely will be mild. You might hear this condition called alpha-thalassemia trait.
If three copies of the genes are missing, your symptoms likely will be moderate to severe.
https://www.mayoclinic.org/diseases-conditions/thalassemia/symptoms-causes/syc-20354995#causes

 

[Oliver3]

Why? It should have no significant effect on my life. It can't reduce my chance of getting malaria, since that's already effectively zero here in Alberta.

Hmmm, I should have said "thalassemia trait", since there's another more severe form that I think is usually fatal. I just have cells with 3 hemoglobins rather than 4 (or something like that).

Ahhh you did t tell us about this

 

[SWAlexander]

Ahhh you did t tell us about this

Can you show me a link where I made a mistake?

 

[Mary]

Is there a similar condition in which people have oversized blood cells? If so, are PWME who have that more severe? Do people with that have ME-like symptoms? Just a thought.

MCV stands for mean corpuscular volume. If red blood cells are larger than normal, it very often indicates B12 and/or folate deficiency. My very good doctor (who is no longer with us) explained to me many years ago that the red blood cells get larger to try to compensate for the B12/folate deficiencies.

I had been taking B12 for many years with no noticeable results (but assume I would have been worse off without it) but when I added in methylfolate in 2010, I had a really nice increase in energy. And my MCV was always high normal.

ETA; btw, the folate did nothing for my ME/CFS (PEM, etc.) BUT it did make me feel better in between crashing though it did not extend my energy envelope. If that makes sense. B6 also helped some, as well as B1, which I started later.

People who have larger than normal red blood cells because they're deficient in B12 and/or folate could have fatigue, the usual symptoms of people who are deficient in these nutrients. but they're not ME symptoms.

"Could smaller red blood cells be a missing link in ME/CFS, fatigue, and thalassemia?"

Smaller than normal red blood cells can also indicate iron deficiency anemia. From AI:

A Mean Corpuscular Volume (MCV) blood test measures the average size of your red blood cells. It's a common part of a complete blood count (CBC) and helps diagnose and monitor various conditions, particularly anemia. [1, 2, 3, 4, 5, 6, 7, 8]


What MCV Reveals:

• Normal MCV: Indicates red blood cells are within the typical size range. [1, 2, 9]
• High MCV (Macrocytosis): Suggests red blood cells are larger than normal, potentially due to vitamin B12 or folate deficiency, liver disease, or certain medications. [1, 10]
• Low MCV (Microcytosis): Indicates red blood cells are smaller than normal, possibly due to iron-deficiency anemia or thalassemia. [1, 11]

How MCV is Used:

• Anemia Diagnosis: MCV helps classify different types of anemia based on red blood cell size. [1, 2]
• Monitoring Treatment: MCV can track the effectiveness of anemia treatments. [6, 12]
• Investigating Other Conditions: High or low MCV can also be relevant in conditions like liver disease, vitamin deficiencies, and even some cancers. [5, 6, 10]

Important Considerations:
MCV alone is not a definitive diagnosis.
It's usually interpreted alongside other blood tests and your medical history. [5, 6]
High or low MCV doesn't always mean a serious problem.
For instance, some individuals with Down syndrome may have naturally larger red blood cells. [9, 11]
If your MCV is abnormal, a healthcare professional will determine the next steps.
This may include further testing, lifestyle changes, or treatment. [6, 12]

 

[Oliver3]

Can you show me a link where I made a mistake?

Sorry, I think wires were crossed. This was for ' it's a couple of cells in the brain' guy wishful

 

[SWAlexander]

Wishful​

Did you mean to say you have the thalassemia trait, which is the mild, carrier form.

The “3 hemoglobins instead of 4” part is a misunderstanding — they likely meant they’re missing one of the four hemoglobin genes (probably alpha genes).
The severe/fatal form you’re referring to is when all 4 alpha genes are missing, or in severe beta-thalassemia.

Cells with 3 hemoglobins instead of 4" — what does this mean?

This part is a little confused — let me explain what you might be trying to say:

Each hemoglobin molecule is made of 4 protein chains (called globin chains):

Normally: 2 alpha chains + 2 beta chains = HbA (adult hemoglobin).
In thalassemia, there's a problem making either the alpha or beta chains, depending on the type:
In alpha-thalassemia, there are usually 4 alpha genes. You can be missing 1, 2, 3, or all 4.

In beta-thalassemia, there are 2 beta genes — 1 from each parent.

So you might be thinking of alpha-thalassemia trait, where one or two alpha genes are missing:
Missing 1 gene → silent carrier (no symptoms).
Missing 2 genes → alpha-thalassemia trait (mild anemia).
Missing 3 genes → Hemoglobin H disease (moderate to severe anemia).
Missing 4 genes → incompatible with life (usually fatal before birth).

So, when you said “cells with 3 hemoglobins instead of 4,” you probably meant:
They only have 3 working alpha-globin genes, instead of the usual 4.

That would match alpha-thalassemia trait (if two genes are missing) or Hemoglobin H disease (if three are missing).

Reference:
Thalassemia: Alpha & Beta-Thalassemias, Genetics, Pathophysiology, Diagnosis & Treatment, Animation

 

[Wishful]

The “3 hemoglobins instead of 4” part is a misunderstanding — they likely meant they’re missing one of the four hemoglobin genes (probably alpha genes).

Just checked the wiki (I last looked into thalassemia over 20 years ago). My hemoglobin molecules are missing one of four globin chains, making my blood cells smaller. My doctors assured me that there would be no significant effect on my health from that. BTW, the genes don't need to be missing, just defective.

 

[Artemisia]

I inherited thalassemia minor from my dad. My dad has some fatigue issues (similar to what I had before I got ME), but not so much that they have slowed him down or made him quit activities even in his 70s. It seems very different from ME type fatigue and symptoms.

But... maybe there is some kind of link with ME and smaller blood cells. I don't know either way.

 

[Wishful]

But... maybe there is some kind of link with ME and smaller blood cells.

Maybe my smaller blood cells is why I didn't get the usual physical limitations from my ME. That would be a good use of AI: ask questions (requiring tedious searching of huge databases) such as "Do PWME and smaller blood cells have lower physical symptoms than PWME with larger cells?" I'm not sure that the existing data on PWME has much recording of blood cell size.