Tag: hereditary Haemochromatosis

Low Parathyroid Hormone – Hypoparathyroidism?

~ quantumdreamer ~ Leave a comment

The results for the three different mutations of HFE gene are in. I don’t have any of these. Which excludes the vast majority of the diagnoses for hereditary haemochromatosis. The footnote from the lab suggests contacting the centre for rare iron related disease in the big university hospital 150 km away. They may just talk with me as an ex-boffin.

I do feel a tad rusty these days, like the tin man my joints could use some oiling.

That means the polycythaemia primary or secondary question is in focus. Is there a malignancy or did my blood just adapt to smoking tabs?

My parathyroid hormone (PTH) is low, it is 26 pg / mL.

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“The iPTH reference interval of a healthy blood donor population was measured as 25.2–109.1 pg/mL (2.7–11.6 pmol/L) at 2.5 and 97.5 distribution percentile. The iPTH reference interval from data stored in the laboratory database was 19.3–112.5 pg/mL (2.0–11.9 pmol/L). Furthermore, 60% of the whole population had prevalently insufficient vitamin D concentration (<30 ng/dL; <75 nmol/L).

Mineri et al., Clinica Chimica Acta Volume 521, October 2021, Pages 1-8.”

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So it is at the rare end of a distribution yet just within the 2.5-97.5 percentile range. It is probably within experimental error out of the range. The error bars on 26 picograms must be big in a small sample!!

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“PTH is secreted primarily by the chief cells of the parathyroid glands. The gene for PTH is located on chromosome 11. It is a polypeptide containing 84 amino acids, which is a prohormone. It has a molecular mass around 9500 Da”

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My results for Calcium and Phosphorus were very normal, this latter statement is a bit weird. Low PTH levels are very rare and usually come with low Calcium levels. That pathway is messed up. Low parathyroid hormone screws with the Calcium concentration and bone turnover.

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Symptoms of hypoparathyroidism

Hypoparathyroidism often starts if glands in your neck are damaged during surgery.

Symptoms include:

  • a tingling or burning sensation in your fingers, toes and face
  • muscle pain, stiffness and spasms

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I have these two but these are caused when Calcium is too low!! So I do not have hypoparathyroidism.

We have another “contradiction” of sorts so the GP has asked advice from an endocrinologist. My guess would be re-test and if the value is still low maybe do something.

I am going to have an Alpha 1 Antitrypsin assay tomorrow which may add a piece to the jigsaw puzzle, concerning my lungs.

I’ll wait to hear from the GP as to what the endocrinologist suggests. It could be more tests, or not.

On the GP front we are probably good until September now…fingers crossed…

The working notion is that whatever it is that may be going on, it is just not manifesting in a sufficiently serious way, yet…

It could just go away or it could develop.

I am a bit of an anomaly, so it is no surprise that my blood results are a tad skewed from the normal.

Am I a Mutant?

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Tomorrow I am going to have genetic testing for hereditary haemochromatosis.

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“Haemochromatosis is caused by a faulty gene that can be passed on to a child by their parents.”

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“Predictive testing of individuals who have a family history of HH, in coordination with appropriate genetic counselling

This test detects the 2 common disease-causing variants in the HFE gene: C282Y (c.845G>A) and H63D (c.187C>G). The S65C variant will be reported only when it is observed as part of the C282Y/S65C genotype.”

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I have signed the form and given permission for any blood left over to be used for research purposes. I can’t undo the test nor unsee the results and if I am indeed a mutant there is a legal obligation for me to tell relatives in France. I can ask the GP to do this, if I want.

According to the NHS the disease is caused by a “faulty” gene, a bad pair of Levis. NHS speak is not always the most helpful and it is aimed low.

I will find out if I have the X-factor soon and if I can join the mutant army.

Because I have a proper nanna disease, osteoporosis, I am also having a whole bunch of other tests on my Thyroid function done.

Yesterday because we had mole sign, I set traps down by the edge of the pond. Today we went for a walk along a beach. Both of these are getting harder. In two weeks, I will find out if there is a possibility / likelihood of being able to have replacement hips. It is difficult to imagine what life might be like with some flexibility and reduced pain. There is no guarantee.

People selling hip surgery quote statistics like these:

“In general, the success rate for hip replacement surgery is high: About 95% of patients experience relief from hip pain. In one study, HSS interviewed patients to learn about their progress. Two years after their surgeries, 99.4% of patients said they had relief from pain, 98.8% said their ability to move was improved, and 97.8% said their quality of life was better because of their surgery.”

Because I am worth it…there is no big U for Unilever.

The Arthritis foundation says:

Pain Before and After Hip Surgery  

  • 90% – Of patients who had moderate pain before their first surgery reported mild or no pain after five years.  
  • 89% – Of patients with severe pain before their first surgery reported mild or no pain after five years.  

Limitations After Hip Surgery 

Some patients still have limitations after total hip surgery in activities like walking, climbing steps and getting in and out of a car. Seven percent of patients with moderate limitations and 20% with severe limitations before their first surgery still had severe limitations after five years. Among those having revision surgery, 13% who had moderate limitations and 30% with severe limitations reported severe limitations after five years – so 70% were doing well. 

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This is not such a rosy picture. I am on the younger end of the age spectrum despite officially qualifying as an “older person” now. This data is not age weighted. Given my level of medical comorbidities, I don’t have to worry about living another twenty years, so I will probably only need one set of joints. It clearly is not a universal holy grail or panacea for hip osteoarthritis.

In some sense I will have to place a bet. I will be betting that the surgery can happen, that it works and that I recover. I am betting that it will not kill me. My guess is that the second operation will be harder to handle and the likelihood of death during and afterwards higher. I am betting that I will feel better and more able, eventually, post-op. It will take a lot of time.

If I have HH I will probably be getting bled on a regular basis too.

It is possible that I may have some more fun to add to the medical merry-go-round pencilled in for summer. Colonoscopy, prostate PSA levels too high follow up {un toucher rectal} and French rheumatology are all in my diary upcoming. I need to have a full dental survey to rule out infection before I start on bisphosphonates for my brittle bones.

Blood tests often lead to more blood tests…maybe my Thyroid is shot too!

Hey-ho…

It would be a lot easier to take me out the back paddock and shoot me….

Genetic Counsellors and Cans of Worms

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I learned a new phrase today “genetic counsellor”. Apparently, at least in Canada, such things exist. I have been recommended to have the HFE gene test to see if I have hereditary haemochromatosis (HH). This for completion. Back in 1994 I visited this high haemoglobin “space” and was bled regularly at St Thomas’. Retrospect suggests that I may have had an ongoing health condition which was missed back then.

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They took an armful each time. 

This HFE mutation would provide a benign explanation for my raised haem and ferritin levels. My ferritin levels have been increasing with time over the last four years. I don’t really have many of the symptoms associated with the genetic disease. It is linked with the less benign polycythaemia. Which would require a wider more substantive gene panel test, so-called molecular oncology. The authorisation for this testing is probably reserved for specialists. Iron overload is not without consequences. It can “cause” cancer or be correlated with it. Medical literature often blurs correlation with cause.

The problem with all this new-fangled gene testing is that it can open a can of worms

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Needless to say, the genetics are complex.

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I would be a mutant of sorts…

The next stages are Iron MRI and/or liver biopsy. The latter does not sound like much fun!!

Liver disease is possible maybe even likely, but I am largely asymptomatic. My enzyme work was ok.

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The next stage of inquiry would be to look for myeloproliferative neoplasms which are rare, not lottery winning rare, but rare enough. Search of JAK 2 and other related things starts increasing the price. JAK 2 can mutate.

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“Mutations in JAK2 have been implicated in polycythemia vera, essential thrombocythemia, and myelofibrosis as well as other myeloproliferative disorders. This mutation (V617F), a change of valine to phenylalanine at the 617 position, appears to render hematopoietic cells more sensitive to growth factors such as erythropoietin and thrombopoietin, because the receptors for these growth factors require JAK2 for signal transduction. JAK2 mutation, when demonstrable, is one of the methods of diagnosing polycythemia vera.”

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The thing is looking closely at most people my age the chances are that you will find something which has gone wrong.

The French sites suggest that some kind of follow up is warranted because of my Iron status.

Not sure what if anything the GP will recommend….

The osteoporosis situation seems simpler to treat with some pills, supplements and vitamins. But could have an Iron cause.

Given that the haemoglobin situation has been ongoing for, perhaps, thirty years it seems unlikely that any new unpleasant things have suddenly taken hold. But the ferritin level has doubled since 2021.

There is part of me that thinks that I just let this all drop…The osteoporosis might have enabled the fracture of my femoral neck six years ago. I have perhaps been living with it since. Simple answer is to not fall over.

A few more pills is no big deal however…

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hereditary haemochromatosis – regularly being bled.

Not HH – Iron MRI / Liver biopsy —

Liver disease – it depends on what – treatments in absence of virus are usually diet and no booze.

Something fancy and esoteric – myeloproliferative neoplasms – massive complex can of worms

The French sites suggest that some kind of follow up is warranted because of my Iron status.

What is inside the can…?

Reasons to be Cheerful – Iron Two and Three

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We heard on the news today that Netanyahu had a colonoscopy this morning. This means that he would have been on an industrial grade laxative protocol last night and this morning. He will have a sore sphincter and maybe, just maybe, he is now less full of shit. He has quite a few comorbidities. He is not renown for joviality, good will or a good sense of humour so the indignity of shitting his entire arse off may not have appealed to him. Laid out on a table with a metre long endoscope up your arse it is hard to be tough, macho and aggressive spouting bellicose propaganda.

Did you know that a single article in the Lancet can cost you forty quid!!

It turns out there is specialist research interest in excess bodily Iron in Rennes, particularly for rare Fe related genetic diseases. We just took the car to the garage and there was an advertising card “Jardin du Fer” so we are back roaming the streets and chanting “any old Iron” like pikeys in a white flatbed truck.

One of the guys from Rennes is a co-author:

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One of the problems and benefits of having been a researcher in a previous incarnation is the ability to scan-read to spot gaps in knowledge and then zoom in, on the off chance there may be a research proposal lurking. The primer paper suggests the following diagnosis flow chart. I am on the far right pathway. All genetic testing is expensive.

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On the basis of this I am possibly due an Iron MRI. Apparently, the presence of Fe changes the T2 nuclear relaxation time and by using various pulse echo sequences one can measure Fe content in the liver. One can also image Fe content relative to the spleen. The latter is more widely used.

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The Fe build up could be genetic, alcohol related or caused by primary or metastatic cancers. The gastroenterologist said they stopped following liver for metastatic disease five years after colon cancer. This being the most likely hang out for colon metastatic disease.

The corporeal symptom of hemochromatosis are given below.

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Hepatomegaly (Enlarged Liver) An enlarged liver is a symptom of underlying disease. It means that your liver is larger than normal. This may happen in response to an infection, advanced liver disease or cancer. Healthcare providers treat an enlarged liver by treating what’s causing it.

I have joint pain and have just added Osteoporosis to the fun list.

The default cause will be ethanolic, followed my smoking with my being a lard-arse a close third.

Maybe I am not special…maybe it really is that simple…

My research instincts say there may be something we are missing and have yet to find out about.

Reasons to be cheerful… Iron two and three.

Bioethics, Genetic Testing and Notification

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This morning, just for a change, we went to another hospital for a genetics follow up to the wife’s breast cancer. In France they are very keen on prophylactic measures and like to test things in a lab wherever possible. The wife’s blood is going to be screened for genetic predisposition to breast and ovarian cancer. The results will have implications for her and her siblings, including the men. In French law the geneticist or the wife herself MUST inform her brother if the tests suggest that he too might have a predisposition for cancer. This true for if he lived in France not sure if it extends legally to the UK. The form letter on the government site, for the geneticist to fill in, does not really hide the identity of the provider of genetic material very well. Today she advised against sending this. It was better to pass on the tidings of joy personally.

« Décret n° 2013-527 du 20 juin 2013 relatif aux conditions de mise en œuvre de l’information de la parentèle dans le cadre d’un examen des caractéristiques génétiques à finalité médicale.

Notice : la loi no 2011-814 du 7 juillet 2011 relative à la bioéthique a modifié le dispositif d’information de la parentèle dans le cadre d’un examen des caractéristiques génétiques introduit par la loi no 2004-800 du 6 août 2004 relative à la bioéthique. La personne concernée est informée, avant la réalisation de l’examen de ses caractéristiques génétiques, de l’obligation qui pèse sur elle, au cas où une anomalie génétique grave serait diagnostiquée, d’informer les membres de sa famille potentiellement concernés dès lors que des mesures de prévention ou de soins peuvent leur être proposées. »

The gastroenterologist following my colon cancer has been very pushy about me notifying blood relatives because there is some genetic component to colon cancer.

I have already tested for HBA B27 which was negative therefore there are no requirements for notification. There are no possible interventions foreseen.

I am considering HFE and JAK poly screening, the latter of which costs ~€1500. The HFE if positive would indicate hereditary Haemochromatosis which can have interventions. The JAK poly screening for predisposition to malignancies, would if positive, require notification. There would under law be an obligation to inform.

This explains why the GP isn’t overly keen. There is a possible can of worms attached.

The documentation for the test today has inherent in it an authorisation to share genetic test results with relatives if relevant to their healthcare.

Given the price of the test, I am likely to need a specialist to write the JAK screening prescription. They may well want a “who do you think you are” family tree.

You learn something every day…and given the French love of protocol this is non-negotiable.

There are often implications we do not consider…and only find subsequently.

Once you have had test results you cannot un-have them or un-see them…

Hmnn…