This week, I’m catching up on recent journal articles related to chronic hypophosphatemia. First, a caveat that I said a few months ago that researchers and editors seemed to have gotten better about not conflating XLH with rickets, but I may have been premature in announcing that that issue had been fixed. You’ll note that some of the articles listed below show a decided backslide to using the inaccurate and lazy “form of rickets” language.
On the plus side, there are articles that get the nomenclature and all the patient-focused details right, like this one, “The International X-Linked Hypophosphataemia (XLH) Registry: first interim analysis of baseline demographic, genetic and clinical data” (pre-print). It makes sense that researchers who work closely with a wide range of patients on topics that include patient-reported outcomes would be careful not to use patient-harming language. Seriously, though, isn’t this a great, accurate, modern, non-harmful description of XLH?
X-linked hypophosphataemia (XLH) is a rare, hereditary, progressive, lifelong, phosphate-wasting disease resulting in continued accumulation of musculoskeletal manifestations
I also found it interesting that they noted an apparent reduction in the delay in diagnosis over time, presumably due to milder cases getting a correct diagnosis in childhood, rather than, as used to happen, in adulthood, especially when a child is diagnosed, which leads to an undiagnosed parent getting a diagnosis. (Although see this story from Rare Disease Day about a meteorologist who has XLH, and wasn’t diagnosed until adulthood, which is a variation on stories I’ve heard from several XLHers who were only diagnosed after they had a child with more severe symptoms.)
Another interesting article, “Intact Fibroblast Growth Factor 23 (iFGF23) Concentrations in Hypophosphatemic Disorders” offers some potentially useful information for correctly diagnosing the various chronic hypophosphatemias based on FGF23 lab results, which are less expensive than genetic testing, and therefore may provide answers when genetic testing is out of reach for a given patient. It’s been reported in the past that some XLH patients have “normal” FGF23 blood levels (despite the excess in the kidneys), making them useless for diagnosis, so this research was an attempt at fine-tuning the test results, looking for patterns that could indeed indicate a correct diagnosis. It’s a bit too advanced for me, but appears useful for those who cannot obtain genetic testing. (If you’re in the U.S., free genetic testing for XLH may be available through either Ultragenyx’s or Kyowa Kirin NA’s patient support programs. Link to the Ultragenyx option is here. I don’t have one for Kyowa Kirin yet.)
I had to grit my teeth to read “Impact of X-Linked Hypophosphatemia on Muscle Symptoms” because of the conflation with rickets — ironic in an article pointing out the non-bone symptoms! But it’s good to see our non-bone symptoms getting some attention, with a conclusion that encourages more research into the muscle issues.
“Sex differences of burosumab in children with X-linked hypophosphataemic rickets” purports to show that male patients may need a higher dose of burosumab than female patients, although I am skeptical, due to the tiny number of patients (ten), and a variety of other factors (different ages, severity, specific mutations). Or perhaps I’m just biased by the conflation of XLH with rickets, which suggests the authors don’t have the really extensive experience with XLH that would make me trust their conclusions.
“X-Linked Hypophosphatemia … Is Often Misdiagnosed as Ankylosing Spondylitis and Manifests in Both Men and Women” doesn’t offer anything new for patients (I’ve frequently heard from patients who were told they had ankylosing spondylitis, and I was misdiagnosed with it myself), but it’s good to have the error pointed out in a peer-reviewed article. It’s one of the misdiagnoses that I believe Dr. Erik Imel was referring to in his closing summary at the Symposium on Hypophosphatemia, when he noted that ignorance of the full range of adult symptoms from chronic hypophosphatemia leads to a search for additional, unnecessary/incorrect diagnoses, wasting both time and money.
A few years ago, there was an article that concluded the old phosphate/calcitriol treatment had a small benefit for XLH patients’ dental issues, but not on the progression of calcifications. A new article, “Effect of conventional treatment on dental complications and ectopic ossifications among 30 adults with XLH,” confirms that conclusion.
And finally, there’s a new article on growth hormone: “Growth hormone treatment improves final height in children with X-linked hypophosphatemia.” There’s long been debate over the appropriateness of HGH (Human Growth Hormone) treatment for XLH, with one camp being concerned that it would worsen the disproportion seen naturally (normal torso in comparison to shortened legs), with the other camp discounting that concern. The article doesn’t address this issue, unless I missed it, perhaps because it was a retrospective study and the proportional measurements weren’t available, just the overall height. The issue might become moot as more data is collected for patients who have reached their full height after being on burosumab throughout childhood (the hope is that they will achieve a normal height due to the better mineralization than the old phos/calcitriol treatment), but the current data isn’t clear on the benefits of burosumab for height. Personally, I don’t really care about height, as long as burosumab strengthens and straightens our bones, etc., but to the extent height matters, this article confirms that HGH does produce increased final height for XLH patients who were particularly short despite superficially good treatment with phosphorus/calcitriol.
It’s really impressive how much research is happening for #XLH (and it’s starting to happen for ENPP1 too), compared to just twenty years ago, when the scientific community first became aware of the discovery of FGF23, the key to understanding XLH (and some of the autosomal and tumor-induced hypophosphatemias). I can barely keep up with it all!
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Please note that the author is a well-read patient, not a doctor, and is not offering medical or legal advice.
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