Purple Canaries

Joyce Gould with Jill Gould

NPAW (National Porphyria Awareness Week) Caregiver Commentary, Friday, April 12, 2019

Latent; clinically latent; completely latent; asymptomatic; completely asymptomatic; totally asymptomatic; clinically expressed; overt; manifest; biochemical and clinically manifest.

Over the years, many terms such as these have been used by doctors/scientists to describe patients’ acute porphyria activity (most notably AIP which has long been the scientific “darling” of the acute porphyrias). In 1994, based on results from urine testing and enzyme assays, a UK study team used the following AIP activity classifications: manifest, latent, normal to assess a study group of twelve patients.Individuals who had a past history of an acute attack of porphyria with documented biochemical confirmation were classified as manifest cases. “Latent cases were defined as individuals who at the time of interview or documented in the past had biochemical evidence of raised urinary porphyrins combined with a porphobilinogen deaminase activity at least 2 standard deviations below the mean but never had a clinical attack. Normals were defined as the family members in whom the PBG deaminase was within normal range, with no evidence of increased excretion of porphyrins in the urine and no clinical history suggestive of an acute attack.”(1)

That same article noted that Dr. Waldenstrom of Sweden (recognized as the “father” of AIP”) had “discovered in asymptomatic relatives the excretion of porphyrin metabolites in the urine [and] described these individuals as latent cases in a 1937 study.”(1) However, two years later, Dr. Waldenstrom reported he had observed “a case where porphyrins could be detected neither in urine nor bile during an attack.”(2) He continued, “The diagnosis: porphyria without porphyrins and chromogen was discussed. Its correctness has now been proved.” He did note, however that “porphyrins and red pigment were found in the [patient’s] urine at a later date, when the patient showed no abdominal symptoms…and added, [t]wo brothers of the patient suffer from typical a.p.”(2) Unfortunately, I was unable to locate the term Dr. Waldenstrom might have applied to the patient he’d observed in an attack that did not excrete porphyrins or chromogen. So, in my book, I referred to my daughter who has suffered severe acute porphyria symptoms and attacks, but hadn’t excreted porphyrins or chromogens as having “atypical” AIP. I knew, as a mother does, that my daughter had an acute porphyria. DNA proved me right. But an APF-associated porph expert claimed her AIP was latent. No thanks to that non-profit “patient advocacy” organization, I was referred to a Swedish born, bred and medically trained pediatric hematologist/AIP expert. She recommended an aggressive treatment program that saved my daughter’s life. Five years later, the geneticist who’d granted the diagnosis revoked it altogether. On top of everything, one non-medico “expert” had the gall to tell my daughter, in writing, no less, “…it can be very difficult to obtain a diagnosis. We have several patients in the same situation with DNA but no attacks.”

There are tens, perhaps hundreds, maybe thousands or more patients the world over who suffer with “porphyria without porphyrins and chromogen.” Acute Porphyria “kicks their butts” every single day. It is well past time that SOMEONE acknowledge Dr. Waldenstrom’s assessment and all these patients that APF et al has erroneously (and caustically) labeled each of them “latent,” “asymptomatic” or “misdiagnosed” and designate an applicable, appropriate term to identify porphyria [attacks] without porphyrins or chromogen.

If anyone would like links to the above footnotes, just leave a message.


NPAW (National Porphyria Awareness Week) Caregiver OpinionThursday, April 11, 2019

 

 

If anyone has doubt about APF’s agenda to keep acute porphyria rare, here’s something from an 2018 Alnylam Pharmaceutical Earnings Call Transcript* in which an Alnylam executive assured a querying investor, “let me emphasize that porphyria will remain an ultra-rare disease…we’ve been working with the porphyria network to strengthen the next set of physicians….” Yup, train a gaggle of physicians in how to dismiss the huge and growing population of “atypical presentation” (decidedly NOT rare) acute porphyria patients; how to ignore (not build upon) the prior “greatest generations of Porphyria scientists/experts'” findings; how to gaslight patients, physicians and society; how to get away with HIPAA violations and so much more–but most important of all–how to keep acute porphyria in the “NIH rare and ultra-rare disease zone.

Leave a message at www.purplecanaries.com if you’d like the actual link.

 

*Q2 2018


NPAW (National Porphyria Awareness Week), Tuesday, April 9, 2019

This NPAW, thought I’d share bits of history uncovered as I review, sort and file zillions (ok, not zillions, but a lot) of porphyria-related articles.

Orange–hued urine…acute porphyria attacks associated with severe heme depletion in the liver….

U.S. Dr. Cecil J. Watson (1901-1983)’s medical fellowship was completed in the Munich laboratory of the world’s leading expert in the chemistry of hemoglobin, bile pigments, and porphyrins, Nobel laureate Dr. Hans Fischer. Dr. Watson had developed a keen interest “in the formation and structure of the various heme derivatives which are formed in the intestine from bilirubin and are in part reabsorbed and re-excreted in urine or bile.” He is credited with proving that excreted porphyrins represent intermediates formed in the course of heme synthesis, whereas the tetrapyrroles of the urobilin group are degradation products of heme formed by stepwise microbial reduction of bilirubin in the intestine. One of his early findings showed that when bilirubin has reached the intestine, it is almost quantitatively converted to colorless derivatives by the intestinal microflora. On oxidation, these chromogens turn into bright orange pigments, several of which [he] succeeded in crystallizing.”

It was Dr. Watson who recognized that acute porphyric attacks are associated with severe heme depletion in the liver—hmmm, exactly what Jill and I have observed ourselves for years. In 1941, he and his coworker Schwartz developed the classic Watson-Schwartz test for qualitative detection of urinary PBG .

Retirement didn’t stop this Energizer bunny-scientist—“ he had the unique intellectual satisfaction of discovering a highly effective and often life-saving therapy for a disease which had preoccupied him for over forty years—the successful treatment of acute porphyric attacks with the infusion of hematin (heme replacement). Yet another “proof” Jill and I have observed for years.

In reading a review of this exceptional yet humble doctor who wasn’t above “riding the ambulance which, at that time, was a duty assigned to assistant residents” and lament that that era of U.S. porphyria scientist is long gone.

Source available by leaving a message at www.purplecanaries.com.


Monday, National Porphyria Awareness Week April 8, 2019

Acute porphyria is… “horrible.” “excruciating, mind-bending pain, and more pain, vomiting, heart racing like crazy, not being able to breathe, brutal—just brutal.” “being treated like or talked to like you’re a hypochondriac, a junkie or mentally ill.” “doctors acting like I’m crazy.” “being told over and over that ‘everything’ is normal—but I know it isn’t.” “very isolating, very scary and very, very painful.” “not understood.” “losing friends, jobs, life, self.”

Acute porphyria is… “never being believed—by anyone.” “being treated with contempt by doctors, families.” “ERs, hospitalization, no answers, no help, no interest.” “seeing umpteen doctors who just don’t give a f-ck…don’t give a sh-t…don’t listen…don’t believe you…just don’t care.” “like being in a warped ‘Alice in Wonderland’ story.” “like wrangling unicorns.” “a life shredder.” “involuntary commitment to psyche wards—the worst.” “praying that the next attack won’t be my last—but will be the one when I finally pee pbgs.”According to a discerning Australian-based porphyria specialist, “Porphyria* is as bad as cancer.”

With the exception of the medical expert’s assertion, the foregoing metaphors were offered by people who suffer with acute porphyria, or caregivers who bear witness to the physical, neurological, emotional, financial and societal degradations that accompany acute porphyria manifestations. While the first sequence of metaphors can be universally attributed to all acute porphyria patients, the second set reflects the more hopeless tone voiced by patients whose acute porphyria diagnoses have been withheld (directly or indirectly) or revoked (in the U.S.) by experts associated with the American Porphyria Foundation (APF).

Undoubtedly, APF is the dominant force in the U.S. porphyria arena. The non-profit is revered by most patients who receive an expert-authenticated acute porphyria diagnosis yet is reviled by those who fit virtually every aspect of the diagnostic mold except one—they don’t excreted massive amounts of certain biochemicals (U-BP) during porphyria attacks. (Or as some allege, APF experts “moved the goalposts” over the years.) The second paragraph of metaphors reflects the more grave responses by devastated patients who were/are summarily discounted, dismissed and left to their own devices by the U.S. “porphyria patient-advocacy and physician-education” organization—because they don’t “pee pbgs.” This group of hapless patients is ever-expanding and was dubbed “Misfit Porphs” by an intrepid individual who herself was burned APF et al’s inhumane treatment.


Saturday, National Porphyria Awareness Week, 2019

 APRIL 6 – 13, 2019

NATIONAL PORPHYRIA AWARENESS WEEK

Finally! An organization that understands…

The New York State Rare Disease Alliance:

A Place for Patients and Caregivers Who are the True Experts in Rare and Complex Disease Care

This is why Closed Facebook Forums dedicated to Porphyria were established long ago and have continued to flourish and expand for years. These pages offer honest insight and support because the individuals truly are experts in knowing their own bodies and/or in the case of caregivers, in providing accurate information in support of these patients when porphyria is afoot. The forums are also where APF acolytes snatch helpful information not available to them on the “experts” pages–some have even been know to appropriate ideas and claim them as their own.

Thank you to the many brave individuals–patients and caregivers–who established and/or monitor these closed forums. They offer a safe place to fall for newly diagnosed patients and those victimized by wizards behind curtains.


We dance round in a ring and suppose, But the Secret sits in the middle and knows. – Robert Frost

To all my porph friends—patients, caregivers, their friends and family members,

I apologize for having fallen off the face of the earth for a while though I tend to do that when the porph devil’s dancing in Jill’s liver and overdoing things again.

Because of that, I’ve been back on the exhausting documentation trail—and once again, making progress for her and others though, yes it is truly frustrating. In response to a FB closed forum participant’s request, I had conducted a patient survey (very delayed) and thought I’d put a pretty good report together when the sh#t hit the fan. Jill’s AIP has led me yet again to more (“new” to me discoveries) and while it’s been intensely trying for me (never mind her—the patient!!! and those medicos who want to believe but can’t because 1) the diagnostic information they are fed is erroneous and 2) as Robert Frost said, “We dance round in a ring and suppose, But the Secret sits in the middle and knows.”

If you haven’t heard yet, there are two stories of APF devotees connected to the Alnylam Pharmaceuticals’ Givosiran clinical trials you should know about. One has AIP (“expert-confirmed”) and excretes mega-U-BP during attacks so was readily accepted into the clinical trials where she by all accounts has been doing so well she was elevated to an “esteemed” position—an Alnylam Pharmaceuticals spokesperson. The other hasn’t been so lucky. She, too was an “expert-confirmed,” (HCP) APF devotee—so devoted, she’d actually come to U.S. to “learn” APF’s methods, such as they are. However, when time came to enter clinical trials, her U-BP didn’t cut the mustard. She was denied access to the Givosiran clinical trials. Sad to say, her condition deteriorated and I’ve heard she is dying. Why? Her U-BP isn’t good enough. So, essentially, her expert-confirmed diagnosis was yanked and she’s left to die. Sickening, no?

I have finished the “porph-psyche” paper, titled “Acute Porphyria is not “all in your head.” It’s in your blood and liver….” I’m very far behind in FB messages but will be posting this latest paper on my book website, www.purplecanaries.com. It is sure to raise Cain once again. Oh well. I will share the piece first with the anonymous closed forum participant who so long ago asked me to conduct a closed forum patient survey and who’s waited so patiently for it to be finished. I received some wonderfully brave input. Kudos to all those who responded with information to this intimidating topic. I live for the day when our collective voice is heard—and the nefarious individuals contributed to the aching bodies and hearts for decades will finally reap what they have sown.

I thank patients, caregivers, (Moms & Friends), God, angels (heavenly and earthly) and saints, the universe for the all the inspiration and help that has come my way. Dr./Atty. Philip Reilly wrote in his book, Orphan: The Quest to Save Children with Rare Genetic Disorders, about “concerned parents…who have become disease experts.” He also quoted Sir Archibald Garrod who said, “the first great advance in treating rare human inborn errors of metabolism began because of the persistence of a heartbroken, but dedicated, mother and the curiosity of a young physician-scientist.” I haven’t as yet come across a ‘physician-scientist’ but fully intend to persist in this situation. There are too many unacknowledged porphyria patient like my daughter, not only in the U.S. but throughout to world allow it to continue. The U.S. sad state of affairs concerning the acute porphyrias is akin to “playing with fire.” I for, one, don’t play with fire—except when it comes to shooting flaming arrows at those who have such blatant disregard for human life.

 

 


Porphyria Awareness Week – Tuesday, April 24, 2018

Well, well, well. Seems something has gotten under the skin of some porph ivory tower dwellers and hangers-on. Mama Canary doesn’t kowtow to manipulative gaslighting—and knows what she reads. Methinks this individual and her followers need to review what “she” herself wrote in her 2014 memoir —and what she wrote nine years later. To clear up a few things: I know full well that back in the day, porphyria was unlikely to be a blip on any differential diagnosis list and biochemical testing was not used routinely—until after APF was established (that’s fodder for future post). If I said “she” “had negative test results for ten years before [“she”] was diagnosed,” it would have been in the context of relating to the vast majority of “misdiagnosed” acute porphyria patients’ diagnostic odysseys.

I’ll start with the memoir—as “she” says, straight from the source. “She” is the one who opened her book with the statement, “I was only seventeen when I suffered my first attack of Porphyria.” (pg2) Understandably, “she” had no knowledge of familial porphyria (another upcoming post)at that time. However, many of the undiagnosed/misdiagnosed people do have bio-family members with porphyria and/or DNA confirmation. Yet “she” proceeded to tell, or was complicit in telling, so many who are in the same position she had been in from age 17-27 (or as “she” says now, 18-28) that their attacks aren’t porphyria because their U-BP levels are not high enough during attack. Seriously?? Obviously “she” didn’t excrete U-BP—apparently not until after she’d become a mother and noticed “at times I voided strange looking dark urine” (pg 13). She did not disclose in her book if this “strange colored urine” was ever captured during her many forays to various doctors, or if it happened when she experienced attacks. However, she did note, “nothing could be done for me in light of the lack of biochemical indicators” (pg 11) so I suppose not, because docs/lab would likely have noticed the atypical nature of the urine and investigated it. Bottom line, it is assumed the APF index case had acute porphyria sans urinary biochemical proof (U-BP) for about 10 years.

She can credit “her” “mild seizure activity” (pg 19-20) for her 36+year AIP position. For that’s what lead to “her” ingesting a dose of Dilantin. And that lead to, “Fortuitously, the urine bag rapidly filled with what appeared to be…purple-red…urine. (pg22) Perhaps ‘she” can clarify when it was decided that in order to be diagnosed with porphyria, patients had to excrete excessive amounts of U-BP? And answer the question, did she or did she not have porphyria before she swallowed that Dilantin? According to her book, she learned, after that pre-Dilantin period (via blood tests) that bio-family members also carried the genetic defect, but that too is fodder for yet another post.

It’s going to be a long week of installments. The Purple Canary flock has lots to impart. We ask that you read—and make your own decisions.


Home Genetic Tests May be Riddled with Errors… UPDATE…REQUEST UNDERLYING DATA FOR ALL DNA TEST RESULTS!!!!

On 4/3/2018 Huffpost published an article about home genetic tests titled “Home Genetic Tests May be Riddled with Errors, and Companies Aren’t Keeping Track” written by Anna Almendrala. It’s a great title; really draws attention. But it doesn’t tell the full story of how to find out if a snp is active or not. I emailed Anna and shared this information, thinking she might tell the couple profiled in the article about it. Thanks to my beautiful friend, Ellen Asher’ guidance, I learned the key to finding whether snps/rs are pathogenic or not is to download 23andme’ raw data to a third party DNA sequencing program (I used Livewello; there are others) and select the illness template you are interested in. I selected the Porphyria Panel. That generated a full Porphyria Panel (Jill’s was eleven pages with more than 100 SNPs/rsID numbers for ALAD, ALAS2, CPOX, FECH, HFE, HMBS, PPOX, UROD, UROS) based on the 23andme raw data. This will provide you with SNPs per gene indicator (i.e. HMBS for AIP) and rsID identifiers. Using the rsID numbers, access ClinVar (https://www.ncbi.nlm.nih.gov/clinvar) and enter the rs#. ClinVar will generate a full report about that particular rs# that even novices can understand. Perhaps the most important category sought is Clinical Significance. Jill’s ClinVar Clinical Significance results ranged from Benign (the most); Likely Benign; Conflicting interpretations of pathogenicity and Pathogenic. Very interesting to say the least.

I was informed by a high ranking, “in the know” genetic scientist/data analyst that not all genetic labs (even the most “reputable” among them, in fact all APF-connected labs) comply with contributing data to ClinVar’s international database. This of course leaves holes in what has become an important though dynamic diagnostic tool with is patently unfair and, in my opinion, completely irresponsible.

Also, since this post was originally made, the issue of patients specifically requesting ALL underlying (aka supporting) documentation (including rs#s) for every DNA test results s/he may have submitted to has come to the forefront. This is important to do no matter how long ago the test was done. One should not feel squeamish about requesting the data. It is yours, and according to HIPPA law, you are entitled to it–within 30 days of request as a matter of fact. Parents can request their minor children’s data. Upon receipt, ClinVar results are there for the taking–at no charge. Simply follow the directions above and you will be able to verify that the provider’s test results match. If they don’t…request a full explanation, in writing.

Remember the entire medical industry is in “hurry-up, I needed it yesterday” mode. Competition among genetic labs

is fierce—and getting even more so. Sniping at competitor’s data is going to continue. Try to find a non-biased geneticist to review the information with you. Somebody recently posted a wonderful phrase on a FB forum: “DNA is a destiny, not a destination.” Love it! Genes set the mood, but gene expression results from a host of endogenous and exogenous factors. When it comes to your body, experience trumps experiments. Do what’s best for YOU.


REAL HEROES: THOSE WHO SUFFER WITH UNRECOGNIZED ACUTE PORPHYRIA

If anyone wants to learn about real heroes, all one has to do is tune into closed FB porphyria forums. Tossed aside because they haven’t achieved a “real” diagnosis (as Desiree Lyon Howe articulated during the March 1, 2017 FDA/APF meeting—evidentially to her, “real”  means confirmed by APF “experts”), these remarkably brave patients cope with the same challenges (debilitating symptoms but no biochemical proof) Desiree Lyon Howe was freed from at about age 27. That’s when she swallowed a Dilantin tablet (capsule?) prescribed by an unsuspecting doctor that induced a life-threatening attack which produced purple-hued urine and voila—the diagnosis of AIP which ultimately led to the establishment of the APF. One has to wonder how (or if) she would be faring today had that Dilantin never materialized and she had been left ad infinitum with symptoms as participants of these forums are. Excepting, of course, the APF members who are encouraged to “help spread the cause” by bringing these “poor souls” into the APF “light” so troll these closed forums, if not for that purpose, then to report back to the mother ship and/or bully closed forum administrators about “unfair” posts. To the real heroes on this and other closed forums, please know that your life and experiences do matter—and someday (soon, I hope) your voice will matter too. In the meantime, perhaps this article, written by another hero, Ellen Smith who suffers not with porphyria but with Ehlers-Danlos Syndrome and Sarcoidosis that may help sustain and support you through this day. http://nationalpainreport.com/living-my-new-normal-life-with-chronic-pain-that-i-dont-want-defining-me-8835779.html [Special thanks to Barbara Bradbury Wilcox for leading me to the National Pain Report forum.]


A telling story for all patients with atypical acute porphyria presentation.

    • If the illness doesn’t kill you, the medical bills just might.
    • Look elsewhere for answers.
  • For an eye- and mind-opening information (and review of a documented case history) , check out 2018 STILL FEAR-RIDDEN, FRUSTRATED, FORGOTTEN AND FED-UP: Patients with Atypical Acute Porphyria Presentation STILL Stuck in Urinary Diagnostic Quagmire