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Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.
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Ritux has helped with lessening of symptoms overall, I can tell during the last month before each treatment that its worn off.
Can you quantify that improvement in symptoms in terms of where you were on the ME/CFS scale of: very severe, severe, moderate, mild, remission before rituximab treatment, and where you are on that scale after treatment?
Have you moved up by one level on that scale (eg, moving from severe to moderate, or moderate to mild)? Or perhaps moved up by a half level?
fatigue- very severe and its improved to severe/moderate.
So when you say your fatigue and PEM were very severe before rituximab, you are saying that you were bedbound 24 hours a day, except for a few minutes each day to go to the toilet?
Very severe ME/CFS means bedbound 24/7.
Not quite that bad except maybe the first couple times I had PEM in hot weather, had to stay inside the house to recuperate for a couple of days just sleeping and not moving.
So maybe you had severe ME/CFS, rather than very severe? Severe is where you are in bed most of the day and night, but up for a severals hours a day, probably mostly on the sofa, maybe watching TV or using a laptop. Would that better describe you before rituximab?
And after rituximab, would you say you are now at the moderate level of ME/CFS? Moderate means you are out out bed all day (except perhaps for a nap for an hour or two during the day), but still fairly housebound, and don't leave the house much.
Why have you been on rituximab for 2 years? Why is your physician giving you a medication that is not indicated for ME/CFS?
Distal hereditary motor neuronopathy 2D (HMN2D)
Synonyms:HMN IID; NEUROPATHY, DISTAL HEREDITARY MOTOR, TYPE IID; SPINAL MUSCULAR ATROPHY, DISTAL, AUTOSOMAL DOMINANT, CALF-PREDOMINANT
This sequence change affects a donor splice site in intron 9 of the FBXO38 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FBXO38-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in FBXO38 cause disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
I interpreted what @pogoman said was this could be a coexisting illness with ME/CFS but Kaiser in the US does NOT recognize ME/CFS as a treatable disease. Kaiser is one of the largest medical groups in the US and it has NO physicians for ME/CFS, and rarely allows patients to see doctors outside of their group. So in effect Kaiser does not recognize ME/CFS.So you are saying you think you are probably not an ME/CFS patient?
I don't have ME/CFS, its not a diagnosis in the US and especially for Kaiser Permanente HMO that I'm a member of.
What I have is an unknown non-inflammatory myopathy in my right leg found by muscle biopsy in 2014, the year I joined this forum.
The working diagnosis is necrotizing autoimmune myopathy and ritux is one of the main drugs of choice for NAM.
I've already done ivig and methotrexate the past few years, ritux has helped the most.
NAM was almost unknown when I was diagnosed, Dr Christopher-Stine at John Hopkins led research into it when statin users started getting muscle damage after stopping statin drugs.
This also reminds me of my Invitae myopathy and nuero panel lab tests I had done in 2017 and 2018 by Kaiser.
I had several variants of unknown significance, for one of them the FBXO38 gene my test results made it into the NCBI Clinvar database.
With the muscle loss and now spinal issues starting to appear I am wondering if this is the actual disease.
Unfortunately until there is further research into this gene I won't know, thats why its a VUS.
If you click on the evidence tab this is what my test results state.
So you are saying you think you are probably not an ME/CFS patient?
I interpreted what @pogoman said was this could be a coexisting illness with ME/CFS but Kaiser in the US does NOT recognize ME/CFS as a treatable disease. Kaiser is one of the largest medical groups in the US and it has NO physicians for ME/CFS, and rarely allows patients to see doctors outside of their group. So in effect Kaiser does not recognize ME/CFS.
My experience in the US has been that doctors don't generally believe in CFS as an illness. In Kaiser that is a fact as described by many patients.
@pogoman, your illness seems quite serious and complexe, involving both neuropathy and myopathy.
Sometimes, I feel it may be better if docs doesn't care about the ME/CFS diagnosis, it may provide more opportunities for investigations ...
FBX038 gene mutation can produce Distal Hereditary Motor Neuropathy. It's a peripheral large fibers neuropathy.
Do you know if you had nerve conduction velocity testing showing any defect?
@pogoman The gnomAD database (genome aggregation database from the Broad Institute) shows 1 person with this variation in the European, non Finnish population cohort database .
There is a high confidence prediction that the variant leads to loss of function (pLoF)
View attachment 38410
I see it links to my Clinvar results page but its incorrect about lineage and sex.
On my fathers side its generally northern European and on my mothers side its Japanese and I'm male.
How is sex determined for gnomAD samples?
We used a combination of X-chromosome homozygosity (F-stat, impute_sex function in Hail) and X and Y chromosomes normalized coverage to assign sex for each gnomAD sample. Note that we used different combination of metrics (mostly due to their availability) for the different gnomAD datasets (see below for details). The F-stat was computed for each sample using high-confidence QC SNVs (bi-allelic SNVs, LD-pruned to r2 < 0.1, with allele frequency > 0.1% and call rate > 99%) on non-pseudoautosomal regions (non-PAR) of the X chromosome. The normalized coverage was computed as the mean coverage on sex chromosomes / mean coverage on chromosome 20. The exact metrics and threshold used for sex assignment were as follows:
- Genomes (gnomAD v3):
- Males: chromosome X (non-PAR) F-stat > 0.2 & 0.5 < normalized X coverage > 1.4 & 1.2 < normalized Y coverage > 0.15
- Females: chromosome X (non-PAR) F-stat < -0.2 & 1.4 < normalized X coverage > 2.25 & normalized X coverage < 0.1
- Exomes (gnomAD v2):
- Males: chromosome X (non-PAR) F-stat > 0.6 & normalized Y chromosome coverage ≥ 0.1
- Females: chromosome X (non-PAR) F-stat < 0.5 & normalized Y chromosome coverage < 0.1
- Genomes (gnomAD v2):
- Males: chromosome X (non-PAR) F-stat > 0.8
- Females: chromosome X (non-PAR) F-stat < 0.5