Purple Canaries

Joyce Gould with Jill Gould


April 16, 2018National Porphyria Awareness Week – Saturday, April 21, 2018


Being dealt a bad genetic hand is tough—especially when the illness involved is an invisible one. Porphyria Awareness Week runs from April 21st through April 28th. The Porphyrias are a group of genetic illnesses known as inborn errors of metabolism. Living with an acute porphyria is gritty, real and raw. Because every single molecule that enters the body is metabolized by the liver, the acute porphyric patient lives precariously day to day and sometimes during those days, minute to minute. Ain’t nothing easy about it. Metabolic issues surrounding acute porphyria can be unexpected, mystifying, brutally painful and horribly isolating for the patient. For observers, symptoms appear nothing short of bizarre. It is not at all unusual for patients to be accused of faking, looking for attention, drug seeking or being a hypochondriac—even by people with higher education and professional training who should know better. But some don’t. Lacking an anthropological education, I can only speculate why in the 21st century society has not yet fully discarded the primordial act of shunning the sick or incapacitated among us.


National Porphyria Awareness Week – Sunday, April 22, 2018

On this, the beginning of Porphyria Awareness Week, I’ve got a proposition for the sycophants—let the mothers among you speak. If you are not the mother of a child who has suffered and been handed the mocking “misdiagnosed” label, please keep your thoughts locked up tightly in that empty ward. It is quite obvious that members of both camps live with acute porphyria misery. But mothers of atypical acute porph patients are not the ones whose “misinformation” may kill a vulnerable person. Uncaring, malevolent inaction has a better chance of accomplishing that.


National Porphyria Awareness Week – Monday, April 23, 2018

We’ve been called nonsense social media sources, trouble makers, over-protective, helicopter, Munchausen by Proxy mothers. We were recently accused of spreading misinformation, risking the lives of “vulnerable people” on the open Facebook forum, Porphyria Sucks. As mothers, we are determined. No one’s opinion means more to us than our daughters’ health does.


National 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 led to “her” ingesting a dose of Dilantin. And that led 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….


Porphyria Awareness Week 2018 – Wednesday, 4/25/2018

I remember feeling scared yet oddly secure when I read “Porphyria, A Lyon’s Share of Trouble” years ago. Because what the APF executive director described in her memoir—porphyria symptoms and attacks but no “lab proof” was exactly the position my eleven then twelve year old daughter was in (except she struggled with frequent grand mal type seizures—not “mild seizure activity.” Finally, I thought, someone who understands. Unfortunately, that feeling of security was supplanted when APF et al all but dismissed my daughter health concerns. The scared feeling escalated, joined by frustration.

Thanks to the Internet, I met the mother of a young-adult daughter who offered a referral to a Swedish born, bred and medically trained/US transplanted pediatric hematologist /AIP specialist who was treating her daughter for acute porphyria. Long story short, this doctor confirmed that Jill’s AIP was active—and that it required hemin treatment ASAP.

Fast forward to 2013. Things were abuzz at the national voluntary health organization (per NORD). APF announced that the president of Alnylam Pharmaceuticals had made an “exciting presentation” at the International Congress (Switzerland that year) about the drug company’s development of a potential RNAi therapy to treat acute porphyria attacks (APF 2nd Qtr 2013 newsletter). “Research: key to your cure!” was the edition’s theme. APF members were urged to consider volunteering in any or all of a number of studies. Though it was not clearly articulated in the newsletters, APF, Mount Sinai and Alnylam Pharmaceuticals had established a business Triad.

But it was the 4th Quarter, 2013 newsletter that ultimately raised radars. Alnylam was afforded an article to describe more about the ALN-AS1 therapy and its intent to “directly commercialize [it] around the world.” Interested patients were invited to contact APF. Great—as I said earlier in the week, porphyria is pure medical misery and anything to reduce or eliminate such misery should be championed. However, three pages later in that same newsletter, appeared “Lyon’s Share,” the focus of which was a not-unheard of—a non-profit necessity of beating the bushes for donations with empathetic appeal. But the spiel contained a puzzling re-boot of Ms. Howe’s memoir. She wrote, “I remember being so afraid when I had my first attack of AIP. I was in terrible pain and so sick I was sent on an air ambulance to the NIH in Washington, DC. There I was seen by an expert who gave me Hematin therapy every day.” According to her 2004 book, these events did happen—but only after she’d taken the dose of Dilantin, approximately ten years after her reported “first attack” at age seventeen—which had not resulted in Hematin therapy. Same person, different version. What the heck?

Eventually, with research, the mists began to clear and the dots to connect. Alnylam. Mount Sinai. APF. U-BP (Urinary-Biochemical Proof). That’s why the ASHE (Asymptomatic High Excreters—sort of an oxymoron) were the highly sought-after first group of “subjects.” Dr. Desnick’s genetic lab team had relied on U-BP to test the effectiveness of ALN-AS1 in animal models; Alnylam is doing the same with since-named Givosiran [https://clinicalrials.gov/ct2/show/NCT0333816 pg. 3] Gotcha. The bloom came off the ALN-AS1 rose. “Misdiagnosed” acute porphyria patients don’t have a chance in hell of benefiting from Givosiran—at least not in the U.S. But hey, they don’t suffer with porphyria. Right?


National Porphyria Awareness Week 2018 – Thursday 4/26/2018

APF has dedicated “this week to promote this group of rare diseases, reduce the stigma associated with porphyria through physician education, and provide support for those affected.” Porph mothers collectively note that “those affected” means only patients confirmed by APF-connected experts. That is, patients who produce excessive amount of biochemical proof in urinary excretions during potentially life-threatening attacks. Hmm. So let me get something straight. The AHSE (asymptomatic high excreters) who don’t have attacks but excrete massive amounts of U-BP are revered but the patients who suffer severe attacks and chronic symptoms but don’t make the U-BP grade are shunned? Has the APF EVP ever considered that had it not been for that dose of Dilantin, there’s a good chance she would found have herself amongst the crowd of undiagnosed patients still seeking help?

That’s the issue stuck in the mothers’ craws. Over the 36+ years of APF’s existence, the number of patients dismissed by this patient advocacy organization because of U-BP has steadily grown. Yet the pool of confirmed patients has remained within rare disease limits—even now with the entire gamut of acute porphyrias (ADP, AIP, HCP, VP) lumped together into the newly touted “ultra-rare” disease category.

One has to ask why, in spite of APF’s years-long efforts, physicians in the general medical community still have little familiarity with acute porphyria. Probably because for the last 36 years or so, once the word porphyria is thought or uttered, APF inevitably enters the picture. And for the “undiagnosed” (or as APF experts refer to them) the “misdiagnosed” that’s when despair becomes devastation. All due to urinary output, according to some porphyria specialists, probably one of the most fallible methods of diagnosing porphyria. APF’s “worldwide” force is largely comprised of European countries. The US/European diagnostic model for all acute porphyrias is highly dependent on U-BP. But there are physicians in this and other countries who don’t rely on U-BP when deciding to treat porphyria. For example a South American team of porphyria experts recently provided a medical opinion about my daughter’s case. Based on enzyme deficiency, they said her AIP is active and requires treatment with hemin. Second time in the 11 years that a non-APF connected porphyria specialist with no agenda but to offer help gave us that answer. Another mother took her daughter to be tested in France. Again, enzyme deficiency confirmed. APF et al rejects the efficacy of enzyme diagnostics, saying DNA is preferred. That will be discussed in closing installments of NPAW commentary.


National Porphyria Awareness Week 2018 – Friday 4/27/2018

DHL’s position of “APF only posts and publishes what our scientific advisory board of experts says,” [APF open FB page 9/16/2016; 10:02 pm] perhaps accounts for muddy porph waters. Diagnosing acute porphyria, as said yesterday, is the first hurdle to overcome. But what to do when messages like this are bounced around:

“DNA …is now the gold standard of diagnosis and is available through specialty labs.” [www.porphyria foundation.com; APF>Home>Testing for Porphyria: Acute Intermittent Porphyria (AIP)] .

“Mutation analysis is the “gold standard” of diagnosis for the acute porphyrias.” [http://www.porphyriafoundation.com/ckfinder/userfiles/files/Porphyria%202.pdf; pg 33]


“Typical diagnosis is measuring PBG and ALA in the urine, sometimes the plasma.” [RJDesnick 3/1/2017 FDA/APF presentation ~3:12:52 on video @ www.porphyriafoundation.com]. He quickly expanded, “There are patients that don’t have ALA and PBG diagnoses…That’s. The. Gold. Standard….and you know, to do a genetic diagnosis is another level but if you are symptomatic and if you’re having problems and your doctor thinks you have it, ALA and PBG in the urine is a simple, not expensive test—and it’s not influenced by a lot.” He then turned the program over to Dr. Anderson (UTMB) “whose lab runs more ALA and PBG than most other places in the world.” [FDA/APF Patient Focused Drug Development (PFDD) Meeting for the Acute Porphyrias, March 1, 2017; ~3:13:52 on video]


“dna tests are gold standard.” [DLH; APF Facebook Page, Open Forum; February 17, 2018 9:16 a.m.]


In response to discussion about enzyme assay, DLH posted (March 20, 2018) on FB Porphyria Sucks open forum, “…dna is best test. We have contacted The French [sic] team because enzyme testing isnt [sic] primary now that dna is used and they say lke [sic] here in the usa that they use dna. Experts worldwide are using dna as its [sic] gold standard to determine mutation.”


A closed Facebook porphyria forum participant recently posted that s/he’d asked Dr. Anderson (UTMB) why “they” didn’t do enzyme assessment. He replied, “because we have DNA.” [~March, 2018]

DNA…U-BP (urinary biochemical proof)…enzyme assay… Left out of this equation/discussions are F-BP (fecal biochemical proof)…heme deficiency…clinical symptoms…identification of sub-types of each acute porphyria (AIP, ADP, HCP, VP).

In 2008, my first foray into porph research, DNA was king. My daughter had not produced U-BP but I knew from researching APF online information that that was important so I dutifully followed suit and asked every doctor, in practice and ER about testing samples. No one knew what to do. One of her earliest (deemed “brown” by the ER staff) was tossed in the trash as I uttered the question. Fast forward several months. We met with the Swedish/US Transplanted pediatric hematologist/AIP specialist who shrugged off the U-BP. “Her AIP is active.” Unlike any of the US, APF-connected doctors, she hails from the area of Arjepolg, Sweden—AIP ground zero—so has intimate knowledge of AIP. NPAW wrap up tomorrow…


National Porphyria Awareness Week 2018 – Saturday 4/28/2018

Apparently enzyme assay was once relied on to define AIP subtypes (I don’t know if the other acute porphyrias were ever delineated as such). I learned of enzyme assessment from Dr. Sassa’s writings about CRIM (crossreacting immunological material) to delineate subtypes, based on PBGD. As it turns out, Dr. Desnick and other APF-associated professionals are very familiar with the CRIM/PBGD connection. To wit, he and Dr. Anderson authored “Characterization of the Porphobilinogen Deaminase Deficiency in Acute Intermittent Porphyria” (1981). Dr. Desnick went on to write and/or contribute to several more articles about the subject.

Ms. Howe noted, “Enzyme deficiency testing is not diagnostic alone. In fact, experts worldwide rarely use it and most are getting rid of it as it doesn’t tell much. We now have dna…the French, who still do the test for specific purposes, say the enzyme test is unreliable and faulty…”

Evidently, the Swedes still occasionally rely on the method. If a patient presents with porphyria symptoms without U-BP but doesn’t appear on their national porphyria database, they conduct enzyme assay to determine treatment protocol. So it does have merit. However, according to an expert source, the LEVEL of enzyme activity alone can provide a diagnosis for AIP. This statement is guaranteed to flip US experts upside down. After reviewing US lab results and experts’ pronouncements provided by me about my daughter’s case, a non-US porphyria expert team disagreed with US claims that she doesn’t have AIP. They instead confirmed her AIP’s “active-ness” and need for hemin with the following statement, “The critical result for a diagnosis of AIP is the level of enzymatic activity of hydroxymethylbilane synthase, whether the patient is presenting an acute crisis or 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 not mandatory. In the presence of typical symptoms, a low enzymatic activity is diagnostic, even with absent U-BP (read paragraph above again).”

DNA testing has entered a wild west type of era. Bio-tech and pharmaceutical companies are tripping over each other to get a piece of the pie initiated by 23andme. Competition is fierce and will get even more so. Ms. Howe is right in correcting me about one thing. Invitae and Alnylam entered into a partnership and are offering free porphyria DNA testing to people who meet certain criteria. I probably had Sema4, a Mount Sinai spin off in mind when writing that one. Doesn’t really matter. But what does matter is that “buyer beware” is urged when hiring a DNA testing company. Results comparison can be a nightmare—and few doctors know what to do with them or how to gauge reliability of the results anyway. Genetic counselors will surely become another step of the acute porphryria diagnostic fiasco.

The last point I’ll address this NPAW is “mental” symptoms and porphyria. While the APF EVP is almost certainly attempting to soothe patients that acute porphyria does not cause “mental symptoms,” that is just untrue. Psychiatric symptoms have been well documented as being characteristic of acute porphyria. In fact, during the first appointment our family had with the Swedish AIP specialist in 2008, she said “whenever someone comes to [ER] at home with “mental symptoms,” the first thing that happens is to test for AIP.” Ms. Howe described in her book how she experienced “convoluted reasoning and confusion” (pg 156) and told of a male patient who was delusional, thinking he was a vampire (pg 134)—these are examples of mental changes. Many, many “undiagnosed” (“misdiagnosed, according to experts) struggle with mental challenges of various capacities. Too many have spent time in mental health hospitals or wards, where because they don’t have a “confirmed” diagnosis, they are without a voice so too often are subjected to unsafe medications which only exacerbates problems. With so many avenues available to diagnose acute porphyria, insisting solely on U-BP has only muddied the waters. In order to reduce the stigma, one must address and embrace it—wholly.


Saturday 4/28/2018 To admins of Porphyria; Diagnosed, now what?; Porphyria Alliance; Porphyria Support Group International Closed FB forums:

Thank you from the bottom of the moms & friends coalition’s collective hearts for graciously allowing me to horn in on your awesome Facebook page this week. I may have been the mouthpiece, but we are all in sync with achieving common goals. We see the suffering, we see the rejection. We too know of the despair and destitution wreaked by malevolence and pledge to work FOR you. We now return you to your page’s regular program and will resume our “normal” participation.