Back before the FDA approved burosumab in 2018, I did a series called “The ABCs of XLH” for the XLH Network. Since we’re coming up on XLH Awareness Day (June 23 in the Americas), I thought I’d revisit the series to see what I might do differently if I wrote it today, five-plus years later.
I’m not sure if it’s good or bad that most of the letters would remain the same. A is still for Arthritis, which which historically, has tended to occur in XLHers earlier than in the general population, presumably due to the way our bones are misaligned when they meet at joints, especially in the feet, legs and hips. I’d have to add a footnote if I were publishing the series today, since now there’s some hope that kids who start on burosumab early (and continue on it in adulthood) will have less arthritis (no more than the general population) due to better leg straightening during childhood.
One big change would be in the second letter. Originally, I used “B is for Balance,” and talked about the need for a careful “balance of phosphorus supplements with a proportionate amount of calcitriol” when administering the only treatment available then. Now, of course, B would be for burosumab (the generic name of what’s known commercially as Crysvita). Balance might be a runner-up though, not so much with respect to the outdated treatment, but to the mobility issues (the risk of falling from poor balance) many of us experience.
The next few letters remain unchanged: I still recommend that those who are new to the community should read the “Clinician’s Guide to XLH” for basic information, with the caveat that we’ve learned a lot since it was first published in 2012. Dental abscesses continue to be a big issue and Endocrinology remains the main specialty treating us. Today, I might substitute enthesopathy (calcification of soft tissue) for endocrinology, since we’re starting to understand more about the enthesopathy process, but we don’t know enough to be able to stop/undo it (yet).
FGF23 is still as early in the process as we can trace the cause (although researchers are looking to go further back, to better understand the link between the genetic variants and how the cause the overproduction of FGF23). Originally G was for Genetic transmission, and an explanation of how X-linked dominant conditions are inherited. Today though, I’d be more inclined to discuss the basics of Gene Therapy.
Hearing issues remain poorly understood in XLH, although there has been some relevant research that may someday offer us some answers. ICD-10 codes are now ICD-11 codes, but haven’t changed for us (83.31 for all the familial hypophosphatemias, but not TIO). As far as I know, there isn’t a code specific to ENPP1, but I wouldn’t be surprised if patient advocates are working on obtaining one.
There’s nothing particularly new on the topics of Joint damage, Kidneys (ours are not defective, just carrying out a defective message), although I might substitute Kyowa Kirin, N.A. for that letter (see below for why). I am seeing some improvement on the Listening front, especially among the younger clinicians, who not only claim to believe patients are the experts, but actually do!
The news is less good for Misdiagnoses, which continue to run amok. I would have hoped to have more Natural history information by now, but at least there’s a strong effort happening now, especially in Europe, to better understand how XLH progresses over a patient’s lifetime.
We still have Osteomalacia, PhEX is still the relevant portion of the X-chromosome where the most common variants are found, our Quality of Life remains impaired (although there’s hope for future generations with burosumab treatment), Rickets continues to be misused to describe XLH (but the usage does seem to be fading a bit, especially among true experts and younger clinicians, and burosumab seems to heal kids’ rickets faster and more completely than the old treatment).
I’d hoped that Standard of care would have improved by now, but there’s still a resistance, as I explained in an earlier post, to acknowledging that 1) the old treatment is terrible, 2) burosumab should be the default treatment, and 3) it should continue throughout life. I also would have liked to see some centers of excellence established by now, but they haven’t happened in the U.S. (at least not officially, although some locations are known for their XLH experience by way of word of mouth).
Treatment, as noted above, hasn’t come as far as I’d have liked, in terms of either moving past the old phosphorus/calcitriol regiment, or looking forward to gene therapy and possibly an intervention that prevents the production of excess FGF23, rather than just blocking it after it’s produced.
U was for Ultragenyx until recently, and we still owe them gratitude for their work in shepherding burosumab through the clinical trial process to commercialization. But they are no longer the distributor, so we need to add Kyowa Kirin, NA to the alphabet, and substitute “Undiagnosed” for Ultragenyx. Kids, especially those with spontaneous variations, still remain undiagnosed for an unacceptably long time (pretty much the same age as in the 1950s, some 70 years ago!), so we need to do more work in bringing phosphorus labs back to the routine bloodwork for young kids.
“V is for Vitamin D” needs a slight update to acknowledge that patients on burosumab sometimes develop low vitamin D blood levels and may need to be on supplements of over-the-counter vitamin D3. (Remember that, despite the old name of vitamin D Resistant Rickets, we don’t necessarily have low vitamin D blood levels as a result of the gene variant, just low levels of the hormone that’s made out of vitamin D.)
I’m still an advocate for reminding clinicians that XLH is a Whole-life, whole-body disorder, but I’ve added whole-family to the phrase now (with thanks to Elizabeth Olear, who taught me the three-part phrase).
X still stands for XLH, although there is one change I’d make to the explanation. The original series gave the number of affected patients as approximately 1 in 20,000 births, and some recent research has suggested it may be more rare than that (although still not ultra-rare, like TIO and ENPP1).
Y is for You and Z is for Zest (for life), and I still believe those are critical reminders of the importance of patient engagement and the enthusiasm for life that I’ve seen in most of the XLHers (and TIO/ENPP1/etc. patients) I’ve met.
Bottom line: no really big changes for the hypophosphatemia community in the last five years, but there have been lots of tiny, little steps that offer hope for the future. Patient advocates will need to keep working to make we don’t back-slide, we can tap into the promise of gene therapy, and that all patients get access to the best possible treatment (or cure)!
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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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