RELIABLE BIOCHEMICAL CRITERIA FOR CONFIRMING AN ACUTE ATTACK OF NEUROPORPHYRIA

N. Schoenfeld1,2 and R. Mamet1

1Porphyria Reference Laboratory, Rabin Medical Center, Beilinson Campus, Petah Tikva, and 2Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

Porphyria experts concur that acute attacks of AIP, VP and HCP, are invariably associated with increases in urinary PBG. Reports differ, however, as to the amount of   increase indicative of an acute attack. Some authors consider excretion of at least 50 mg PBG/day, (25-fold the upper level of normal), as indicative, whereas, others regard   a 10-fold or even a 2-fold increase, as sufficient indication.

An additional diagnostic difficulty arises from the fact that in many individuals known to have inherited one of the acute porphyrias, PBG is persistently raised also during remission. It may be markedly elevated even in asymptomatic carriers.

In the absence of a universally accepted standard for interpreting PBG results, attribution of neurovisceral or neuropsychiatric symptoms in porphyrics to an acute attack of porphyria rather than to other causes, depends largely on clinical assessment.

The aim of this work was to identify reliable criteria, which will enable establishing or excluding an acute attack, on a biochemical basis.

The study summarizes and interprets data obtained during classical neurovisceral acute attacks and latent phases in 20 patients (10 with AIP, 6 with VP, and 4 with HCP). Calculated increases in urinary PBG, with the upper level of normal excretion, (2 mg/day), defined as 100%, revealed an overlap between values in the acute and latent phases, (1 to 18.5-fold and 2.3 to 51-fold, respectively). This overlap indicates that the workup in each case needs to be individualized. We achieved this goal, by using another method of calculation, in which the PBG value measured during an acute attack in a particular patient was divided by the PBG value measured in that patient’s latent phase. Increases of 2.3 to 50.5-fold were obtained, leading to the conclusion that any increase, calculated as above, of 2.3-fold and higher, may be taken as indicative of an acute attack.

An additional finding, demonstrated in the study, which might be useful for supporting the diagnosis of an acute attack, is the distinct emission peak observed at 404/621 nm, in the plasma fluorometric scan of AIP and HCP patients, during an acute attack.  

We conclude that comparison of the urinary PBG level and plasma fluorometric scan in the acute phase to those of the latent phase in the individual patient is the key to correct, accurate and reliable biochemical diagnosis of an acute attack in a patient previously diagnosed as a porphyric. The additional tests required for confirming a patient’s first acute attack, having no data to compare with, are discussed.