Purple Canaries

Joyce Gould with Jill Gould


Information about the porphyrias has been traveling through medical circuits since its earliest presentation—from patients’ anecdotal reports to medical scientific interests to society at large as a blend of anecdote, myth and fact.  According to the Merriam-Webster dictionary, an anecdote is “an interesting biological incident”; a myth is “a popular belief or tradition that has grown up around something or someone” and truth is “the state of being the case: fact”. “Fact” is further defined as “actual…hinges on evidence”. German philosopher Schnopenhaur states, “Truth goes through three stages. First, it is ridiculed, second it is violently opposed. Finally it is accepted as self-evident.” It appears what has been presented as factual information (hinges on evidence) by certain porphyria experts may actually learn more toward the anecdote or myth category.

So far this week, Purple Canary has presented two NPAW Acute Porphyria Patient Odysseys: Variegate Porphyria (VP) and Hereditary Coproporphyria Porphyria (HCP). On deck for Friday is an AIP Patient Odyssey. These patient odysseys often prompted research (sometimes quite intense) into topics that don’t necessarily appear in the patient stories that are presented by various porphyria advocacy groups:


As far as the acute porphryias go, it appears the description “rare” is a misnomer that has been overused for decades. Even Dr. Jan Waldenstrom, the “Father of AIP who named the disease in 1937” six years later determined that the “malady may be found much more often than was previously realized, if it is correctly diagnosed.”(1) This is in the country that has long been heralded as having the largest AIP population in the world. Porphyria “maladies” obviously crossed the ocean to America in the genes of European immigrants and by 1953, American researchers reported, “There have been an increasing number of case reports of the hitherto comparatively rare group of disorders included under the general term of porphyria.”(2) That statement, or variations of it, has been found in numerous medical articles.


A fellow nonprofessional porph researcher pointed out illogical comparisons found in APF’s literature concerning porphyria prevalence and noted, “Consistently “blending” European prevalence numbers is not only misleading, but disingenuous for a US-based operation to do.” She’s right. The organization’s website states, “The exact incidence and prevalence of symptomatic AIP is unknown [in U.S.]. But “in Europe the prevalence is estimated to be approximately 5.9 per million people in the general population.” While there is no report for U.S. prevalence of HCP, VP or ADP, the website notes, “VP is especially common in South Africa in individuals of Dutch ancestry, where it has been estimated that 3 in 1,000 of the white population are affected.[and] It is much less prevalent in other countries.”(3) She concluded, “Since this is the American Porphyria Foundation, why not provide prevalence figures for each of the above referenced types of porphyria?” Of course they should. Interestingly, during his 3/1/2017 FDA “Voice of the Patient” presentation, Dr. Herbert Bonkovsky cited AIP prevalence information for Sweden, Finland, UK & West Europe—and USA (which at 2-5/100,000 (for “symptomatic disease”) was in line with its UK & West Europe counterparts. It was not disclosed where that number came from. Recalling what patient “Mary” said during an Alnylam/Givosiran Roundtable session—reported on NPAW Day 3 Commentary (“one thing to realize is even if they’re all latent, every single one of those is potentially a porphyria patient because all they need is one dose of sulfonamide antibiotics like I had and their porphyria is woken up”).(4) Should that statistic be accurate—and realized, the acute porphyrias NIH rare status might well be in jeopardy.


Maintaining the NIH rare disease category status for the porphryias is critical to these partners for many reasons; financial gain is certainly chief among them. As far back as 2014, an Alnylam press release noted, “The acute hepatic porphryias, including AIP, are ultra-rare orphan diseases….”(5) When, during a 2018 Earnings Call an investor analyst questioned how large of an opportunity the drug Givosiran would be, an Alnylam executive replied, “Let me emphasize that porphyria will remain an ultra-rare disease…we are working with the porphyria network to strengthen the next set of physicians that are coming up….”(6) Fast forward to 2019. An Alnylam executive assured an investor analyst that the number of “active disease patients was estimated to be 3,000 in US and Europe of which 1,000 are recurrent attack patients—obviously a larger number in the rest of the world.” It was emphasized that 5,000 was the “real number.”(7)  Hmmm. Only 5,000 acute porphyrics in the entire world?


All of this leads to the muddled terminology defining the status of one’s acute porphyria which I believe began at the earliest of times (say Hippocrates’ era) when it was noted that some patients (the “sickest”) exhibited severe neurological symptoms and excreted darkened urine. I guess when others (even in the same family) exhibited symptoms, but didn’t excrete darkened urine, they were considered to be “having fits” and/or mentally ill. For clarity’s sake, the definition of Latent is hidden, dormant, inactive; Asymptomatic: absence of symptoms and Active/Symptomatic the exhibiting or involving symptoms. What apparently came to pass is that physicians and the earliest of porphyria experts determined that unless a patient excreted darkened urine, his or her porphyria was not active, but latent. Now this is a huge bone of contention not only between the ever-growing number of patients who either don’t excrete darkened urine during severe neurological attacks, and porphyria experts. It has also contributed to a growing number of doctors who attend to such patients questioning porphryia experts’ integrity. Why? Because in reality, it has been well documented that porphyrns and precursors end up in tissue, the bloodstream and/or are excreted via urine. And there are porphyria experts who contend that the latter piece is not a surety.

  • Acute Intermittent Porphyria: Prompt Response to Therapy with Corticotropin, Janoff et all; 1953
  • Studies on the excretion of porphobilinogen in patients with socalled acute porphyria, Waldenstrom & Vahlquist, 1943
  • APF website
  • Alnyam’s 7/24/2018 RNAi Roundtable: Givosiran, in Development for the Treatment of Acute Hepatic Porphyrias
  • Alnylam 5/21/2014 Press release: Alnylam and Collaborators Publish Pre-Clinical Results with ALN-As1, an RNAi Therapeutic Targeting Aminolevulinic Acid Synthase-1 (ALAS-10 for the Treatment of Hepatic Poprhyrias, in the Proceedings of the National Academy of Sciences
  • Alnylam Pharmaceuticals (ALNY) Q2 2018 Results – Earnings Call Transcript
  • Alnylam Pharmaceuticals (ALNY) Q3 2019 Earnings Call Transcript

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