Purple Canaries

Joyce Gould with Jill Gould

Where is the documentation of the basic research done to support the outrageous diagnostic deviations from the Father of AIP (Waldenstrom’s and his colleagues’) era?

When it comes to AIP (and the other acute porphyrias), porphyria experts (particularly US) seem to have neglected basic research after Waldenström (1906-1996) and colleagues of that era’s findings had been established and documented. Why?

For a disease that was identified 80+ years ago and has garnered the bulk of acute porphyria attention since then, it’s pathetic that on the brink of 2020, the pathophysiology of AIP remains not fully understood and therefore not fully documented. Since its inception, with (very) few exceptions, APF’s “research” has had an obvious pharmaceutical bent which feeds its outreach communique practice of “only posting and/or publishing what our experts say.” Because the acute porphyrias fall under the large and diverse group of genetic diseases known as the inborn errors of metabolism (IEM), the past several weeks have found me researching and communicating with IEM experts. In so doing, I was brought back to Waldenström’s earliest AIP papers in which I reviewed his basic research findings.

For your review and mental digestion, following are some points taken from Waldenström’s earliest basic research findings that are relevant to this (U-BP) discussion. Please bear in mind that Waldenström’s and his colleagues’ focus was on AIP—in SWEDISH patients where commonality abounds in AIP genotype(s), yet his descriptions of patients’ U-BP presentations meet IEM descriptions of variable phenotypes. This has been of interest to the patient population that has been expanding for decades.

Re: PBG:

  • “the amount of porphyrin formed from porphobilinogen is largely dependent on accidental factors;”
  • “[porphryin] is probably formed in the bladder…”
  • “administration of sodium biocarbonate 5 gms daily did not appreciably alter the output of porphobilinogen…the urine kept its normal yellow appearance indefinitely upon standing. [However], boiling the acidified urine at once transformed the porpobilinogen into porphyrin and porphobilin.”
  • “porphobilin and uroporphyrin are seen when the acid urine is left standing at room temperature for some days or weeks”
  • “[i]t is thus evident that the occurrence of porphobilinogen even in minute amounts is a sure sign of porphyria.”

Re: contemporary experts’ insistence that “attacks MUST include U-BP evidence:” [lends credence to unreliability of U-BP as the diagnostic “gold standard” criterion.]

  • “I have been able to observe a case where porphyrins could be detected neither in urine nor bile during an attack…The diagnosis: porphyria without porphyrins and chromogen was discussed. Its correction has now been proved.
  • “variable excretion of [pbg] was observed in four brothers of a family of porphyrics—no porphobilinogen or uroporphyrin could be identified in two [brothers, so] the possibility that the excretion of these substances may be intermittent has to be taken into account.”
  • “there exist cases with only transitory excretion of the pathological substance (porphobilinogen).
  • “We have observed a complete disappearance of the porphobilinogen from the urine in altogether four cases.
  • “The possibility that the excretion of these substances [poprphyrins/porphobilinogen] may be intermittent has to be taken into account.”

Re: “subjective” symptoms:

  • “Case IV had a typical acute severe porphyria with extensive pareses. Case V and VI were only suffering from abdominal colics and rather severe intoxication (internally-generated toxins) but without any involvement of the nervous system.”

[Note: “[E]xtensive pareses” or “abdominal colic…without any involvement of the nervous system” might have made sense in that era but as medical technology progressed, the central nervous system began to be better understood and methods to identify (and measure) CNS involvement were developed. Why porphyria experts didn’t adapt and transfer this knowledge to acute porphyria diagnostics is confounding. “Subjective symptoms” was eventually re-termed “somatic symptoms” (psychiatric connotation). Bestowing this “lazy” diagnosis on someone suffering with acute porphyria—a medical condition with a physical base—can have life-threatening consequences for patients. Even as this is being written, patients are suffering recurrent measurable symptoms indicative of CNS involvement: fluctuations (sometimes extreme) in blood pressure, heart rate, respiration rate, temperature, muscle control, paresis, seizure/convulsive activity and bouts of loss of hearing, speech and/or vision along with the “hallmark” severe unrelenting abdominal and other debilitating bodily pains yet are being told, “it is unclear as to whether the symptoms you’ve been having are due to



Re: correlation between symptoms and U-BP:

  • “It has never been proved that porphobilinogen itself has any importance for the production of toxic symptoms.”

Re: “latent porphyria:”

  • “Cases VII-XI were typical latent porphyrics without subjective symptoms.”
  • “pbg content may be high even in latent porphyria.”
  • documented “cases with pbg in the urine who have never during a long life suffered from any symptoms that might be regarded as caused by a porphyria attack.”

[Note: Over time, this patient category came to be labeled “asymptomatic high excreters (ASHE).” These ASHE patients (oxymoronic syntax) have for decades been of intense interest porphyria experts and are highly prized as clinical trial participants. It seems to defy logic why porphyria experts embrace ASHE patients (who produce no “subjective” symptomatology but excrete excessive U-BP) yet refuse to acknowledge patients who present severe “subjective” symptoms yet excrete no- or low U-BP (IF they can produce urine at all—urinary retention is a documented acute porphyria symptom).

Further, Waldenström and a colleague issued what can be considered a caution:

  •  identified 20 cases that “were regarded simply as excretors of chromogen (porphobilinogen) [and] suspected to be candidates for future severe porphyric attacks; this became true [as they] later [developed AIP/subjective] symptoms.”

Finally, my most recently released Patient/Caregiver Discussion Paper included discussion of (and comparison between) Sickle Cell and Acute porphyria red blood cells characteristics. Waldenström provided his findings on something that had basic research been followed up on thru the years, might have paid huge dividends in the lives of those afflicted with acute porphyria:

  • “A rapid pathological breakdown of some necessary cell constituent containing pyrrole nuclei might result in severe derangement in cell function. The cells are thus deprived of some necessary factor (enzyme?)”

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