How Is an Acute Porphyria Diagnosed?
A comprehensive and complete diagnostic evaluation for porphyria consists of the 5 available specialized tests for the acute porphyria's in the U.S., and genetic testing. The U.S. is missing 2 enzyme tests, and an ALAS1 test at this time so patients may have acute porphyria and may test negative due to the lack of availability of all tests.
Please see cautions below as there is a high rate of false negatives, we give percentages and cautions below.
1.) *Fractionated Fecal Porphyrins (test must be High Performance Liquid Chromatography)
2.) *Blood tests of the Enzymes Porphobilnogen Deaminase, and Aminolevuelenic acid Dehydratase
3.) *Porphyrins Plasma fluorescence scan also called Porphyrins Fractionation
4 & 5.) *Urine Aminolevuelenic acid (ALA) and Porphobilnogen (PBG)
6.) *Genetic testing caution most mutations are family specific, a patient can have a negative DNA test and have porphyria, this happens in 1 of 5 patients with just 1 type of porphyria test according to one genetics lab, this is probably a much higher number, given there are 4 other tests and only the urine test was used).
These are not standard lab tests, we wince when people say "all my tests in the ER were normal", the truth is all routinely done tests were (close to) normal, these aren't routinely done tests. Our organization is in agreement with The Australian Porphyria experts to test each patients blood (enzyme), plasma, urine, and stool.
Please note, it is important to rule out Lead poisoning, and to also carefully check the patient for Anemia's, and cancers, as both are seen to a higher degree in porphyria.
Please see the testing cautions below, Porphyria testing has high false negatives for a variety of reasons.
The "stepwise approach" (recommended elsewhere) is incredibly dangerous as it forces patients to wait for an attack which carries a 5-20% mortality rate, and tests only urine initially, which will miss younger patients, many latent patients, and may miss (a high percentage of) HCP, and VP, in life threatening attacks, according to Australian Porphyria expert Dr. Janus M.D. PhD, and Dr. Blake's, research findings in his paper "Fecal Coporporphyrin Isomers in HCP", and in the drug trial for Panhematin the paper entitled "Porphyria" by Dr Watson noted the VP patient had a false negative PBG test.
A concerning number of HCP and VP patients are well documented in and out of attacks in research papers to never have a positive urine PBG test, it is simply incomplete and dangerous to do only urine testing, it is also illegal in the US, as a non FDA approved test may not be used as a sole means of diagnosis under US Law.
We give cautions and tips below, porphyria is a metabolic disease and false negatives often occur.
*Test name: Fecal porphyrins
(must be a High performance liquid chromatography test or about 30%will be missed),
Total fecal porphyrins the best test for Hereditary Coproporphyria.
*Coproporphyrin (CIII+ CI) dominance, the Coproporphyrin should be no more than 16% of total porphyrins, and not more than equal to that of 24% of proptoporphyrin -Dr. Doss Compound Heterozygous Hereditary Coproporphyria
*Abnormal CIII:CI ratio Blake (caution we have records of several patients who have CI not CIII dominance but are Copro dominant which is abnormal)
*High porphyrins ( 30% wont have high porphyrins)
*A patient may not have all characteristics.
*The sample must be light protected (container wrapped in foil, or black container) immediately, and frozen or refrigerated per labs requirements.
*Please NOTE: Coproporphyrin dominance (CIII + CI) is an ABNORMAL finding (no matter what the lab says, currently no US lab is properly flagging abnormal Coproprphyrin dominance results ) and is only seen in one Acute Porphyria, Hereditary Coproporphyria, *In the paper "Variegate Porphyria", Dr. Anderson found that Copro dominance is seen only in one porphyria, HCP.
Coproporphyrin fecal dominance is not seen in "non porphyric" humans, a normal fecal porphyrins profile according to the paper "Compound Heterozygous HCP" by Dr. Doss is the coproporphyrin (CIII+CI) is 16% of total porphyrins and 24% of Protoporphyrin. Unfortunately US labs are not currently flagging some abnormal results that are Copro dominant but do not have a CIII:CI ratio, it is illegal under federal law to conceal an abnormal result, if you see that your, or your patients results are abnormal, but not flagged, we can help you report the lab to the proper governing body, please reach out to us.
*Patients with HCP may not have high porphyrin excretions in fecal testing per Dr. Blake's paper "Fecal Coproporphyrin Isomers in Hereditary Coproporphyria" 40% of one family with HCP did not have high fecal porphyrin excretion. At least one US lab only fractionates at high numbers, this will miss a large number of patients, approximately 30% according to Dr. Blakes research.
*Children may have false negatives below the age of 12.
Fecal testing in Blake's paper could detect even rather young patients.
Allen in his paper "HCP comparison of molecular and biochemical investigations in large family" found by age 10 a CIII:CI ratio was detectable.
*Treatment success! Kuhnel in her Paper "HCP in Germany" found treating the patient with Normosang infusions of heme (The name for the non US version Panhematin) could reverse the abnormal Coprporphyrin fecal porphyrin profile in patients with HCP.
*Test name: The Porphobilinogen Deaminase whole blood enzyme test is tied with the PBG urine test as the best tests for AIP according to the research paper "196 patients with AIP"
In the US there is currently only 2 of the 4 Enzymes in the Acute Porphyria's that have testing: Aminolevuelenic Acid Dehydratase whole blood ALAD (for ALAD) and Porphobilnigen Deainase PBGD (for AIP). We are working to change this! You can donate to us we are working on bring Enzyme testing to the US for HCP and VP, France does them. Enzyme testing for acute porphyria consists of testing four enzymes. The enzymes that are tested are Aminolevuelenic acid dehydratase (ALAD) for aminolevulenic acid dehydratase deficiency porphyria (ADP), porphobilinogen deaminase (PBGD) for acute intermittent porphyria (AIP), coproporphyrinogen oxidase (CPOX) for hereditary coproporphyria (HCP), and protoporphyrinogen oxidase (PPOX) for variegate porphyria (VP). In those with acute porphyria, the enzyme are deficient by approximately half in a heterozygous carrier in AIP, HCP, and VP, to a almost a full loss of the enzyme function in ALAD and homozygous AIP HCP and VP.