Purple Canaries

Joyce Gould with Jill Gould

Validation!! Enzyme assay necessary to confirm AIP diagnosis w/without US expert “Holy Grail” urinary output.

It is Rare Disease Week on Capitol Hill (2/25-3/1/2018) and I have some great news to share. In the midst of writing my 2018 FFFF white paper (this year titled STILL FEAR-RIDDEN, FRUSTRATED, FORGOTTEN AND FED-UP: Atypical Acute Porphyria Patients STILL Stuck in Urinary Diagnostic Quagmire), I was presented with some game-changing information. There is no a doubt that this information will be soundly criticized and challenged by APF et al.

Attempting to get to the truth of Jill’s AIP conundrum, I have communicated with patients, patients, doctors and specialists from around the globe since 2009. I hope you will all read 2018 FFFF in its entirety (www.purplecanaries.com) because it reveals significant information about the current (aka APF/European) acute porphyria diagnostic model. Scrutinizing enzymes is rarely, if ever considered—I know because I’ve tried. However, received a medical opinion about Jill’s case from the IVIC (Venezuela) porphyria expert team and will share its summary (some of which is in all caps—because it’s that important):

“In summary, we believe that there are enough and clear evidences: enzymatic and clinical ones to sustain a medical diagnosis of AIP regardless of the mutation identification failure, which is a known obstacle found in ~40% of populations worldwide and that the symptoms she presents and her enzyme levels are evidences of acute porphyria crises which should be treated every time, if possible with hemarginate or in its defect with hemin…Plasma PB must be performed during any acute crisis and its level should be found above any value encountered in controls if our diagnostic conclusion is right. Enzyme levels should stay abnormally low.”

“THE CRITICAL RESULT FOR A DIAGNOSIS OF AIP IS THE LEVEL OF ENZYMATIC ACTIVITY OF HYDROXYMETHYLBILANE SYNTHASE, WHETHER THE PATIENT IS PRESENTING IN ACUTE CRISIS OF IF NEVER ONE HAS OCCURRED; THE PERSON IS NONETHELESS A CARRIER OF ONE MUTATION CAPABLE OF PRODUCING AN ACUTE CRISIS. A LARGE PROPORTION OF CARRIERS (UP TO 85%) INDEED NEVER HAD ONE. IDENTIFICATION OF THE MUTATION IS AN IDEAL GOAL BUT IT IS NONMANDATORY. IN THE PRESENCE OF TYPICAL SYMPTOMS, A LOW ENZYMATIC ACTIVITY IS DIAGNOSISTIC, EVEN WITH ABSENT U-BP (read paragraph above again).”

In other words, people, unless an AIP diagnostic model includes enzyme measurement, it is incomplete, as I and others have been saying for years about US experts’ decisions to ignore the enzymatic component.


“Porphyria in Africa” article written in 1958 confirms Waldenstrom’s 1939 findings.

From the 1958 article “Porphyria in Africa” by A.G. Shaper, section titled “The Urine in Acute Intermittent Porphyria”: “To complicate matters, in a recent survey of 80 cases seen  at the Mayo Clinic it was noted that no porphobilinogen was found in nine cases with severe CNS involvement and in six cases with abdominal crisis…It should be emphasized that porphyrin excretions may be intermittent.”  Huh. Does this mean Mayo Clinc “forgot” it has this information–or disregards it to this day? I’m aware of several “undiagnosed” AIPers who will find this VERY interesting–and perhaps support their suspicions questionable responses they received from that august entity.


Resolutions vs Revolutions….

2018 is filled with promise.

 

While I’ve not been super at keeping New Year’s resolutions in the past (and in fact, stopped making them years ago), I promise this New Year will contain revolutions of sorts. In fact, Purple Canary, The Girl Who Was Allergic to School: The True Story of How School Chemicals Unleashed a “Rare” Illness that Devastated A Young Girl’s Life’s release already started the movement. Please stay with me and Jill because we will very much need your input and cooperation. It’s time for purple canaries to be uncaged.


Great things can come in small packages.

As this very wearying year comes to an end and I find myself firmly ensconced in the 2017 holiday season, I realized that an inspiring gift had come via the Internet some weeks ago. Just words, it might seem an obscure, small thing to some, but to others, the 88 words meant someone got the message. They appeared in the September 7, 2017 transcript of an Alnylam roundtable session which featured one the foremost AIP experts in the world, Dr. Elian Sadh of Karolinska Institute in Sweden. She stated, “…As for us working in the field, there are several unmet needs and areas for improvement of this field of hepatic porphyrias. We will have very limited knowledge of this pathophysiology of the disorder as well as the natural history. And international collaborations are needed to answer this question. We need better biomarkers for the disease since ALA and PBG probably are just surrogate markers and the specific levels of porphyrin precursors do not correlate to the disease severity nor the risk for the patient to become recurrent.”

 

Interpretation: 1) “International collaboration are needed to answer this question”—not just Sweden, America, European or groups of other researchers working each in its own vacuum; 2) “surrogate biomarkers” (oh, like decreased PBGD seen in one of the CRIM subtypes of AIP that Jill and I (and Japanese experts) have relied on for years to predict AIP activity?); 3) “specific levels of porphyrin precursors do not correlate to the disease severity” (oh, perhaps because a) it’s a long way and a lot happens from enzyme development to urethra and no one knows exactly what quantity might become lodged in various bodily tissue (maybe most or all, leaving little or nothing to be excreted)? and b) risk for patient to become recurrent (meaning CHRONIC?). FINALLY, an expert is acknowledging that urinary biomarkers may not be the end all to be all in diagnosing AIP.

 

To be sure, 2018 will be an interesting year. Most of you know that Jill’s AIP diagnosis was revoked in 2014 by the director of Mount Sinai’s Genetic Laboratory. Since turning 18, her life has been pretty horrific. I wrote Purple Canary to tell the world that AIP can and does present in children. It was a brutal childhood, but adult-world porph is even worse. So with Jill’s approval, I applied for and was awarded conservatorship over her health needs. Mama JG is back. With a vengeance.


A Tribute

Sitting on your throne,
royal down to the bone.
Some say you deserve the Nobel Prize–
a mirror reflection of their lies.
You wear a crown with horns
while we wear crowns of thorns.
Too many are still fooled by your disguise:
a perfect shape, perfect size, pretty little face with a nasty alibi.
This was the last piece Jill penned before succumbing to addiction. She has faced AIP since 11, had her world torpedoed at age 16 by Desnick’s revocation of her diagnosis, beat heroin and survived the “Florida Shuffle.” She’s back and in the Purple Canary fold. Seems progress is being made in German philospher Arthur Schoepenhaur’s vision: Truth goes through three stages. First, it is ridiculed. Second it is violently opposed. Finally it is accepted as self-evident.
Heme deficiency is an insidious condition. Why are so many porphs still left to languish?

Please feel free to share a story of porphyria w/addiction….


The eye sees only what the mind can comprehend. – Henri Bergston

I know I’m not alone in thinking it highly inappropriate that the apf coalesced around an AIP index case who did not produce holy grail darkened urine “naturally” and then joined forces with a group to set the bar for diagnosing ALL acute porphyrias based on excretion levels of of U-PBG (which, as it turns out, is a “moving bar” because the level to secure AIP diagnosis has increased during the organization’s 35+ year history–as many can attest). A look at the numbers I reported on last week indicates that the majority of acute porph cases produced heightened U-PBG “naturally” during attack; only a handful made it into the “club” based on the administration of unsafe meds that prompted the appearance of the precious purplish urine. Refer to my FFFF paper posted on www.purplecanaries.com blog for more of this “nonsense.”


Misleading? Burn my biscuits!

If there’s one thing that burns my biscuits and prompts me to shut that oven off it is knowing that some entity is being surreptitiously untruthful at another human being’s expense. To that end, my husband Ed and I recently exposed such deceit—by medical professionals no less. While they scramble to try (and I emphasis try) to weasel out of this one, we will proceed appropriately. It’s pretty bad when medical-related entities lie, but then again, I’m not too surprised anymore. After all, been there done that, as many of you know only too well.


Analysis shows majority of “confirmed” acute porphyria patients diagnosed via “natural” excretion of darkened urine.

Hoping to distinguish the method of how “confirmed” acute porphyria diagnoses had determined, I recently analyzed 129 AIP, HCP and VP published cases. The results proved interesting:

  • 60% noted they were diagnosed based on urinary biochemical testing following “natural excretion” of darkened urine during attack.
  • 5% reported urinary biochemical testing of darkened urine following administration of “unsafe” (and unplanned) medication(s), prompting the diagnosis.
  • 4% recounted DNA/blood, urine, or spinal fluid samples resulted in diagnosis.
  • 31% did not disclose diagnostic methods. Note: some patients were diagnosed before the advent of biochemical testing.

Purple Canary Prologue: It is wise to not attempt to corner badgers

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Excerpt from Purple Canary Prologue, pg. 5:

“You have to attack with the madness of a mother whose child is surrounded by predators,” blogger Jonathan Morrow wrote as he urged marketing professionals to fight for their ideas. His statement galvanized me–and jogged a memory: several years earlier my sister and I had attended a metaphysical fair and came upon a woman reading totem animal cards. I paid her fee and hoped for something along the lines of the feline family but a few card turns later revealed that my totem animal was–a badger. Unimpressed, I pushed the thought to the back of my mind. But Morrow’s blog post inspired me to revisit what I knew about badgers. The description of the animal’s protectiveness of their young sue seemed to fit now that I was a other and my young ‘in was being threatened with a rare disease. As peers and adults harassed and assaulted her with their GOTCHAJILL! and WHACK-A-Jill! exploits, I abandoned my stalwart pre-parenting position of expecting children to fight their own battles..”

___________________________________________________________________________________________________

http://www.huffingtonpost.com.au/2017/10/24/wild-badger-sneaks-into-home-impersonates-family-cat_a_23254521/

Wild Badger Sneaks Into Home, Impersonates Family Cat

“He didn’t seem too happy when I tried to move him,” a woman said of the critter, which ate the cat’s food.

25/10/2017 5:37 AM AEDT | Updated 19 hours ago

It there was any actual badgering going on, it was likely from the cat.

A bold badger briefly replaced a family’s pet cat after the wild animal reportedly snuck into a home through a cat door last week, ate the feline’s food and took a nap in the cat bed.

An animal rescue officer with the Scottish SPCA was called to the Linlithgow home on Wednesday after the homeowner discovered the wild animal nestled up in the plush bed, the animal welfare group reported on its website.

SPCA Officer Connie O’Neil, who came face-to-face with the cozy creature, said getting the animal to leave took some effort.

“He had gotten in through the cat flap and had eaten all the cat food before going for a sleep on the cat bed,” she recalled in a post on the SSPCA’s website. “He didn’t seem too happy when I tried to move him but I was able to slide the cat bed round and it was then that the badger noticed the back door was open so [he] made a run for it!”

Though the badger may have played the cat’s role to a T, the SPCA advised people to proceed with caution if they spot such animals.

“Like all wild animals badgers can be aggressive when injured or cornered so we would advise not to go near or touch them without giving us a call first,” said Scottish SPCA chief superintendent, Mike Flynn.

Fortunately, he said badgers breaking into homes is “highly unusual.”

 


Porphyria – If Nothing Else, APF Message Inconsistencies Still Consistent

My days of accepting APF/Porphyria Consortium’s writings at face value ended in June 2014 when my daughter’s DNA diagnose was “revised” by APF SAB member Robert J. Desnick. Based on a conversation that her (new to the case) treating hematologist had with Dr. Desnick, AIP treatments were discontinued until her body produced urinary biochemical proof (significantly heightened PBG) during attacks. The APF executive director later responded to my devastated daughter with “supportive” statements like, “Sorry you’re back to square one,” and “We have several patients in the same situation with DNA but no attacks.” Her words confirmed what so many patient/caregivers had already experienced and warned me of–“this person only parrots what her board of experts declares; none of them believes (nor will say) that our attacks are porphyria related. I soon figured out that the patients the executive director was referring to were not (or no longer) associated with APF–some by their own choice, others who’d been “dropped” by the organization. APF’s message incongruity became just too much for this business marketing consultant turned mom of a porphyric to ignore. More message inconsistencies recently surfaced. Here’s the “set-up:”

A recent APF Facebook post reply stated: “Testing is very complex yet simple. First line testing for aip, hcp and vp is to test urine for pbg and ala. During an attack these porphyrin precursors will be very high. Porphyrins will also be high.” No inconsistency as statements such as these are made multiple times on APF’s website:

  • “If urine ALA, PBG and total porphyrins are normal, it is quite certain that any recent symptom are not due to an acute Porphyria.” [1]
  • “Biochemical testing is the demonstration of increased urinary ALA and PBG, and these values are highest during an acute attack when patients are symptomatic.” [2]
  • “[if] the diagnosis of acute porphyria cannot be confirmed by elevated urine PBG values or DNA testing then it would be concluded that the “attack” is not caused by an acute porphyria” [3]
  • “For AIP – a urine porphobilinogen (PBG) test during an acute attack–the urine PBG level will be very high if the symptoms are caused by an acute porphyria (greater than 5 times the normal value)” [4[
  • “If someone has a mutation in an acute porphyria gene and reports symptoms similar to an acute attack, their urine PBG level should be checked. If the urine PBG level is normal then there is likely another cause to this person’s symptoms. Acute attacks are distinguished from other conditions that cause abdominal pan by very high PBG levels.” [5]

However, as most Purple Canary followers know, heightened excretory biochemical “proof” and the word “attack” are key concerns for those who suffer with atypical presentation of acute hepatic porphyrias and the doctors who try to help them. And that’s where the next inconsistency comes in. APF executive director Desiree Lyon was interviewed by Health Professional Radio’s Neil Howard. The Guest Bio for that interview states, “She [Desiree] suffered her first attack when she was 17.” [6] Attack? A lightbulb lit in my mind and I pulled my copy of Porphyria, a Lyon’s Share of Trouble from my office bookcase. There it was–something I’d apparently disremembered since reading the book years ago, “I was only seventeen when I suffered my first attack of Porphyria. The attack commenced with mild pain in my lower abdomen and quickly intensified to the unbearable point.” [7] Mentions of attacks, lack of biochemical proof and porphyria peppered the book:

  • “…I was in a precarious state and lived on the precipice of yet another life-threatening attack.” [8]
  • “the results of the test were normal in every category.” [9]
  • “physicians could not find anything wrong on their standard lab tests.” [10]
  • “I was in excellent health by biochemical standards…” [11]
  • “…nothing that could be done for me in light of the lack of biochemical indicators.” [12]
  • “during my college years I [experienced] similar [symptoms but] the physicians could not find anything wrong on their standard lab tests” [13]
  • “…important to note here that I had not been diagnosed with Porphyria,” [14]

The book goes on to describe how the intermittent nature of porphyria symptoms continued after Desire became a mother and how she’d begun to void “strange looking, dark urine…” [15] which was merely attributed to her menstrual cycle by doctor and patient. Lab results continued to yield nothing; however EEG results indicated minor seizure activity so the treating physician prescribed Dilantin. Apparently one dose resulted in a full-blown, major attack with hallucinations, respiratory difficulty and worse–but also something miraculous–“the urine bag rapidly filled with what appeared to be dark blood…the purple-red color of port wine similar to blood that has dried on a wound.” [16] After biochemical tests were completed, Desiree was given the diagnosis of AIP. She noted, “…dilantin had caused my life-threatening attack of Porphyria.” [17]

My stomach roiled. While I felt sympathy for the seventeen year old  Desiree who “started crying uncontrollably, convinced I was going to die from an undiagnosed ailment before I ever experienced life on my own as a “grown up,” [18] reading it again all these years later, of course Jill was on my mind. Why would Desiree still identify her pre-diagnosis attacks as porphyria related (without biochemical “proof”) and not my daughters–or the uncounted others “with DNA” or familial evidence of acute porphyria? Since the age of eleven, my daughter has lived Desiree’s pre-Dilantin tale over and over again. Since the beginning of seventh grade, she’s suffered full-blown seizure/convulsive episodes (as opposed to “slight” seizure activity or spinning sensations–she’s experienced those as well) and other AIP symptoms (including abdominal pain). Without Dilantin (but exposed to numerous chemicals in school, she’s experienced attacks with hallucinations, respiratory distress (dipping at one point , I kid you not, to SATs in the 30s to which I immediately demanded O2 be administered), crushing chest pain, sensory impairment and paralysis from the waist down among other really terrifying happenings for a 12 year old. Should Dilantin or similar drug  had  been administered, she likely would not have survived–and I’d still be wondering what had caused her death. But maybe her lab tests would finally have yielded what the experts hold so dear. Like Desiree, Jill has always prided herself on her “sense of independence, responsibility and stability” [19] and also never doubted herself or that her crises were imaginary. Nevertheless, at only age 12, she’d been branded with the psychiatric diagnosis of conversion disorder (which was abandoned when the 2008 DNA results came in). While Desiree was able to return to her studies “and active life as a high school senior” [20], the school environment continually triggered Jill’s AIP, earning her so much verbal and physical bullying that she was transferred out of the school district. When she finally ended up in a charter high school for her senior year, at almost the same age as when Desiree started her AIP “journey” began, and looking forward to a fresh start in college, Dr. Desnick torpedoed her world.

Sadly, far too many porphyria patients have been stuck in what I’ll refer to as “Desiree’s pre-Dilantin era.” Some for months, some for years, some for decades. The vast majority (if not all) suffer the mind- and body-boggling physical, neurological and/or psychiatric symptoms (depression is particularly rampant) that acute porphyrias are known to produce. As happened to Desiree, some occasionally void darkened urine (which is sometimes tested but does not meet the established PBG diagnostic criteria). Yet the APF has the gall to say, “We have several  patients in the same situation with DNA but not attacks”? There have been too many lives shattered. Too many opportunities lost. Too many people marginalized because their porph pee doesn’t make the grade. There is little joy in this atypical acute porphyria community, but much pain and suffering. Virtually all know (in spite of not being “warned” by experts who disavow their health crises) about unsafe drugs so aren’t likely to allow such meds as Dilantin, Phenobarbital of similar drug to pass their lips–but all live in fear that ER personnel will administer “typical” treatments when/if they are unable to advocate for themselves. In saying that, I wonder how many APF patients with “confirmed” (aka “real”) acute porphyria diagnosis naturally produced heightened biochemical evidence versus how many were generated by an unsafe drug enhancement?

That Desiree still refers to her “first attack” at age 17 as being a porphyria attack contradicts the APF SAB guideline requiring significantly heightened urinary biochemical proof to designate a porphyria attack. As a reminder, in revising Jill’s DNA status, Dr. Desnick wrote, “it would be important to obtain urinary porphobilinogen (PBG) and aminolevulinic acid (ALA) if the patient or family member experiences symptoms of an acute attack, such as abdominal pain, peripheral neuropathy, and/or central nervous system involvement.” [21]. So based on the above information, will Dr. Desnick and the rest of the SAB vote yea or nay on Desiree’s propensity to refer to episodes she suffered for the years prior to achieving the momentous Dilantin-enhanced AIP diagnosis as porphyria attacks?

Another inconsistency appears in the Guest Bio used for Desiree for  the Health Professional Radio interview, “In 1982, she founded the American Porphyria Foundation…” [22]. For a time on the “About” section of APF’s Facebook page she was identified as founder of APF, too and I wondered why. According to her book, she and James Young, a friend who had family members with AIP collaborated on establishing and choosing the name for The American Porphyria Foundation. James became APF president [23], Desiree the executive vice president. So technically they would be considered co-founders, the title she’d used for years. In fact, James V. Young is identified as Chairman of APF’s Board of Trustees [24] and if I remember correctly, that appears on APF tax forms as well. I’d been told that James Young was deceased (and stated as such in my FFFF paper); I apologize for not doing better research before making that statement as that may not be the case. In any event, my intent is not to split hairs but to give credit where credit is due. Too be sure, Desiree Lyon  and James Young were pioneers. While Desiree may not have been the first American diagnosed with AIP, she and her partner made good on their inspiration to establish APF. Yet there are too many patients who languish in health conditions similar to “Desiree’s pre-Dilantin area” to be ignored by this organization. But they are. And it’s just inconceivable to me and so many others why that is allowed to continue.

  1. www.porphyriafoundation>Testing for Porphyria>First-line testing
  2. Ibid>Testing for Porphyria>Diagnostic Testing for the Acute Porphyrias – Clarification of Testing Results
  3. Ibid
  4. Ibid
  5. www.porphyriafoundation>Testing for Porphyria>Diagnostic Testing for the Acute Porphyrias – Clarification of Testing Results>The Difference between Active and Latent Porphyria
  6. https://healthprofessionalradio.com.au/american-porphyria-foundation; 10/6/2017.
  7. Lyon Howe, Desiree; Porphyria, A Lyon’s Share of Trouble; Digital Datawerks, Inc. 2004 by Howewrite, Inc.; 2.
  8. Ibid, 8.
  9. Ibid, 3.
  10. Ibid, 5.
  11. Ibid, 10.
  12. Ibid, 11.
  13. Ibid, 5.
  14. Ibid, 9
  15. Ibid, 13.
  16. Ibid, 22.
  17. Ibid, 23.
  18. Ibid, 3.
  19. Ibid, 10-11.
  20. Ibid, 4.
  21. Desnick, R.J; Letter to Dr. Sharon Pool, June 2014.
  22. https://healthprofessionalradio.com.au/american-porphyria-foundation; 10/6/2017.
  23. Lyon Howe Desiree; Porphyria, A Lyon’s Share of Trouble; Digital Datawerks, Inc. 2004 by Howewrite, 215.
  24. www.porphryriafoundation.com>Board of Trustees