Purple Canaries

Joyce Gould with Jill Gould

Patient/Caregiver Discussion Paper: WILL US/EU PORPHYRIA EXPERTS MAKE A MOCKERY OF PRECISION MEDICINE AT ICPP? Exploited/Victimized Acute Porphyria Patients/Caregivers Still Concerned

As porphyria experts from around the world make their way to Milan’s 2019 International Congress of Porphryins & Porphyrias (ICPP), a group of acute porphyria patients/caregivers from various countries awaits the outcome of an ICPP roundtable session, “How to define acute attack of Porphyrias.”  The acute porphyrias are metabolic disorders that fall within the disease category of inborn errors of metabolism (IEM). They are considered rare worldwide, although some porphyria experts challenge that (except in the US, where porphyria experts maintain they are “ultra-rare”). How to define an attack of acute porphyria has been long debated by experts and hinges on a single factor—whether excessive quantities of liver metabolites are excreted in urine (aka urinary biochemical proof, or U-BP) during excruciatingly painful, debilitating and potentially life-threatening episodes.

“In the US or EU, U-BP is the elephant in the room—it can make or break a diagnosis. Acute porphyria diagnoses for the above referenced patients (most from US, EU and southern hemisphere countries) have either been denied (withheld) or revoked because they didn’t excrete excessive levels of U-BP during attacks. Without that diagnosis, patients are almost always denied appropriate treatment, which exacerbates an already hellish existence,” said American Joyce Gould, “I know because my daughter’s AIP diagnosis was revoked in 2014 by the same Mount Sinai geneticist, Robert J. Desnick, who’d granted it 5-1/2 years earlier.” Gould says she located a porphyria expert team from out of US which, based on her daughter’s lab results, disputed Desnick’s findings by stating, “In the presence of typical symptoms, a low enzymatic activity is diagnostic, even with absent U-BP.”

Acute porphyria diagnoses were also withheld from Australian Amanda Ballan’s, American Laura Riddle’s and other mother’s daughters—and myriad other patients. In fact, Gould, Ballan and Riddle suggest that tens, hundreds, perhaps even thousands of desperately ill patients, in spite of symptom severity/frequency, positive genetic test results, or having biological family members with (or who died from) porphyria have been (and continue to be) cast aside without a diagnosis, left to their own devices to suffer the horrors of untreated acute porphyria because their bodies didn’t excrete excessive U-BP on cue. With two children genetically diagnosed with HCP more than a decade ago, Ballan knows this horror intimately. Her younger son excreted U-BP and so was provided treatment; however, her daughter, because she did not excrete U-BP suffered horribly for eighteen long years without treatment. Ballan ultimately located a porphyria expert in that country who eschewed U-BP, tested her daughter via fecal samples —and diagnosed her with HCP.

Determined to get to the bottom of the diagnostic conundrum, these mothers joined an active, online cadre of acute porphyria patients/caregivers turned amateur investigators. Gould said, “It became apparent early on that the American Porphyria Foundation (APF) was somehow implicated.” Puzzle pieces began to fall into place when APF (led in the endeavor by Mount Sinai’s Robert J. Desnick) partnered with Alnylam Pharmaceuticals. APF’s diagnostic mantra shifted to precision medicine (e.g. genetic testing)—with mandatory U-BP confirmation required.” Gould said pulling together a timeline of her daughter’s AIP milestones together with input provided by other investigators and APF’s (and its myriad associates’) activities was eye-opening. “As we followed trail after trail, connections became disturbingly apparent that a US porphyria contingent, comprised of APF, certain members of its SAB, its Porphyrias Consortium and associated Porphyria Centers (labs), its ‘Protect the Future’ physician trainee program, Recordati Rare Diseases (and predecessors Abbott, Ovation and Lundbeck) and Alnylam Pharmaceuticals seemed to be involved in a long-term agenda–leveraging U-BP at its core–to insure that the US acute porphyria patient population remain within NIH rare disease parameters. This all but assures FDA orphan drug consideration for medications developed to treat acute porphyria patients—specifically Panhematin® (Recordati) and more recently, Givosiran (Alnylam) as well access to the extensive range of services and funding provided by NIH and other government agencies. It became glaringly evident that in order to safeguard power, prestige and financial gain the agenda offered, exploitation of hapless, low- or non- U-BP excreting patients had been going on for decades. Because each of these patients had been labeled by the experts as ‘misdiagnosed,’ ‘latent,’ or like my, Amanda’s, Laura’s  and others’ daughters or sons, fathers, mothers, aunts, uncles, nieces, nephews and on and on as ‘not having acute porphyria’ and summarily dismissed, they weren’t counted as having acute porphyria,” Gould stated.

“Evidently, with Alnylam’s backing, the intent was (and is) to expand the US agenda into an “International” contingent,” Gould said. She points to a recent medical journal paper initiated by Desnick and co-authored by 23 other US and EU porphyria specialists (the majority of whom have involvement with Alnylam’s Givosiran clinical trials). Titled “International Porphyria Molecular Diagnostic Collaborative: an evidence-based database of verified pathogenic and benign variants for the porphyrias,” the paper’s introduction refers to precision and genomic medicine as being a critical issue in determining whether a disease gene variant is pathogenic or benign.  However, with about two dozen mentions of “biochemical evidence” laced throughout the paper and the untoward bold spotlighting of her daughter’s acute intermittent porphyria mutation, Gould said, “Clearly, this paper was meant to silence me and others whose genetic mutations were also highlighted—but more importantly for the US porphyria contingent to encourage “international” porphyria experts to get on board with agreeing to require U-BP as the definitive criterion for diagnosing the acute porphyrias. However, I’ve done my research and based on Desnick’s own writings, can show, among other things what is provided in that paper about my daughter’s mutation /genetic results is misleading.” Gould says, “Furthermore, after so many years of AFP et al’s continual deflecting, distorting and ducking, it is interesting that Icahn School of Medicine at Mount Sinai (Desnick’s lab) confirmed in an online column of “Porphyria News” (July 26, 2019) what I figured out early in my daughter’s AIP ‘journey;’ the Japanese reported on re AIP/PBGD in 2007 and the out-of-US porphyria team confirmed in 2018—that erythrocyte enzyme levels are accurate barometers of AIP activity. With those thoughts in mind, Laura took her daughter to France for enzyme testing with heightened acute porphyria activity; her enzymes were decreased—below even a French study subject’s level highlighted in a French paper. Yet French and American experts refused to grant the diagnosis. It will be interesting to see what if anything happens now that Icahn researchers opened a window with the statement, ‘Alternatively, AIP may be diagnosed by demonstration of decreased HMBS enzymatic activity [in red-blood cells].’ All in all, it is known that exposure to chemicals (including unsafe medications and solvents) can trigger U-BP—as transpired decades ago in the APF co-founder’s AIP case. It is also known that U-BP is considered to be highly fallible and that some “international” porphyria experts maintain acute porphyrias are not as rare as thought. With all that being said, our patient/caregiver research group speculates that due to an unfathomable number of exogenous and endogenous factors, it’s highly likely the majority of acute porphyria patient bodies don’t excrete “acceptable” U-BP. Which could play into why experts claim it takes ten or more years (which often involves costly “top to toe” medical tests—multiple times) to achieve a diagnosis. The cost to private and public health insurance providers and societies must be astronomical. Imagine how much money, pain and angst could be saved worldwide if honest, unbiased diagnostic testing methods—with disincentives to manipulate lab results adopted,” Gould stated.

In conclusion, she offered, “As purveyors of worldwide porphyria experts’ writings, our patient/caregiver research group believes many gifted, unbiased porphyria experts/scientists with integrity remain in this world. We urge ICPP professionals to not be cowed by US and its “big pharma” clout/pressure, to look beyond textbook presentations and in true precision medicine IEM fashion, entertain that U-BP is not the diagnostic end all to be all (re-inspect Alnylam 2018 EXPLORE study, Frame 7). Family health history, symptom constellation range, severity and frequency, genetics, plasma, enzyme erythrocyte and fecal testing can surely be sorted out to establish “how to define acute attack of porphyria—indeed, it already has.”


  1. Barbara Bradbury

    Our Australian early expert, Dr Roderick McEwin, whose ten year study (1973, 1975) of all porphyria patients in psychiatric hospitals in Australia believed that the presence of ANY porphyrins was diagnostic (private communication.) As with the publications of many if not most of Australian researchers on porphyria and porphyric pigments, they are not mentioned in the bibliographies of researchers in the northern hemisphere.

    • goulds

      Actually, Waldenstrom and Vahlquist discussed this in Studies on the excretion of porphobilinogen in patients with socalled acute porphyria (1943):”several observers (among others Vannotti) have tried to make estimations of the amount of uroporphyria in the urine. We have been able to show that the amount of porphyria formed from porphobilinogen is largely dependent on accidental factors…[and] “high acidity of the urine favours the formation of porphyrins and porphobilinogen and this causes a very dark colour on standing and consequent loss of porphobilinogen.” They further described ASHE (asymptomatic high excreters) patients (which they termed “excretors of chromogen (porphobilinogen) who later developed such symptoms [that is, they became symptomatic]; cases where excretion of porphobilinogen was “only transitory” and something that the ever-expanding population of US/EU “missed diagnosis” patients have sworn is their case–“complete disappearance of the porphobilinogen from the urine altogther. To that end, Waldenstrom/Vahlquist stated that the excretion of “these substances” may be intermittent. To your above point, Waldenstrom/Vahlquist concluded, “It is thus evident that the occurrence of porphobilinogen even in minute amounts is a sure sign of porphyria.” BAM! It appears that the Australian researchers held to the “father of AIP’s” documented words for quite some time–that is, until US self-proclaimed porphyria “experts” figured out a way to line pockets by ensuring that the number of AIP (and the other acute porphyrias) cases remain within the parameters of NIH’s rare disease category. Sadly, based on the horrific eighteen-year ordeal that Australian mom Amanda Ballan endured with two HCP-afflicted offspring (one male, one female) with different presentations, Australian porphyria “experts” evidently followed the US “jaunt”–and caused unwarranted patient/caregiver suffering, as it does here in the US–and in Europe.

    • goulds

      Swedish scientist, “father of AIP,” Dr. Jan Waldenstrom (with colleague Valquist) determined in 1943 that U-porphobilinogen,”even in minute amounts is a sure sign of porphyria.” At that time, he further deemed the appearance of U-porhobilinogen to be accidental, transitory and/or intermittent occurrences–meaning it doesn’t necessarily present with every attack. Having recognized acute porphyria chronicity, he further noted that “intermittent” was not an accurate attribution for the disease. That these findings (among others) were simply ignored and dismissed tells much about the character of physicians who when the opportunity presented itself, chose to follow a pharmaceutical-paved money trail.

  2. Tommy & Renee Phol

    We work with a rare disease org and to remain remain within the parameters of NIH’s rare disease category to ensure Orphan Drug status there must be less than 200,000 diagnosed cases in the US. A recent article stated there were only 3,000 cases of these porphyrias diagnosed worldwide so to line pockets it would make more sense to falsely diangose 190,000 people and sell them meds they don’t need.

    • goulds

      I appreciate that you “work with a rare disease org,” which means you are obviously not one of the “190,000 people” (hmmm, where’d that number come from?) who’ve been left to fend for themselves to face acute porphyria undiagnosed and untreated). That you mention “A recent article stated there were only 3,000 cases of these porphyrias diagnosed worldwide” is suspect because that number was published by Alnylam Pharmaceuticals not too long ago. It is widely known that the pharmaceutical industry and its academic research partners skirt the boundaries of accepted ethical behavior or manipulate research findings to suit their needs. Perhaps that would explain why a 2015 APF-sanctioned presentation cited “2,543 Acute Hepatic Patients” as being on the APF “Patient Registry.” Perchance, would that 3,000 caseload include the 2543 US patients? If so, are you saying that in the intervening four years, only 457 more were diagnosed–WORLDWIDE? IF acute porphyria diagnostics were done without bias, bona fide PATIENTS would reap the dividends of better health–isn’t that the goal of patient advocacy?

    • Barbara Bradbury

      There appears to be no logic in the motivations behind the emphasis on AIP to the exclusion of the other acute porphyrias abd to a serious overemphasis on OOBG when it may be ALA that is the most offending porphyrin and no doubt not the only one. Well done Tommy and Renee, for using a little arithmetic instead of convoluted logic based on erroneous and outdated assumptions. The prevalence of putting things in little boxes and not daring to look again, to see if they have changed is a dangerous practice, that unfortunately spreads like a virus and sometimes like an Australian bushfire, devouring all growth in its path.

      There appears to be no logic in the motivations behind the emphasis on AIP to the exclusion of the other acute porphyrias abd to a serious overemphasis on OOBG when it may be ALA that is the most offending porphyrin and no doubt not the only one. Well done Tommy and Renee, for using a little arithmetic instead of convoluted logic based on erroneous and outdated assumptions. The prevalence of putting things in little boxes and not daring to look again, to see if they have changed is a dangerous practice, that unfortunately spreads like a virus and sometimes like an Australian bushfire, devouring all growth in its path.
      In regard to the numbers of those diagnosed with porphyria globally, something is very skewed indeed, when our Australian Dr
      Roderick McEwin estimated, after studying porphyria numbers in his ten year study of the sixties and seventies, that there should then be 2000 people with this vastly undiagnosed group of diseases, as Steven Rochlitz PhD, has long maintained.
      Poulos et al 1992, Sydney, claimed 1000-2000 in a total Australian population of 17,500,000
      To portray the porphyrias as all life threatening acute diseases diagnosable only in the emergency room flies in the face of logic yet again. Could there not be a continuum of seriousness, thus validating many of the ” strange” syndromes that have arisen. What if they were all porphyrin tested as McEwin did for all psychiatric patients in his ten year study. Perhaps someone should look at all the studies involving control populations as a preliminary to a large population study to see just how many of the normal population have porphyrins. For that matter, as porphyrins occur in every cell of the body and the disease is a multi system, allbody disease, ANY bodily fluid and perhaps the breath could be used to detect porphyrins.

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