Porphyria Conundrum
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Editorial Porphyria Conundrum Jan Waldenstro¨m spoke of porphyria as the “little imita- failure for whom the question of porphyria arises, al- tor” (when syphilis was the great imitator). This caveat is though a rather small number of patients have this still true today: The clinical presentation may vary widely combination of problems. No major advantage is pro- and may encompass cutaneous and neurological signs posed for the other porphyric problems, and the method and symptoms. Appropriate therapy requires as precise a is not geared to measure protoporphyrin or porphyrin diagnosis as possible. Although the clinical presentation precursors. It is surprising that in five patients with might be telling, as, for example, in porphyria cutanea hereditary coproporphyria (one with skin manifesta- tarda, in which the skin changes are fairly typical, other tions), normal or very near normal plasma concentrations porphyrias can overlap in their cutaneous and neurologic for all porphyrins were found. One wonders what the Downloaded from https://academic.oup.com/clinchem/article/45/7/932/5643254 by guest on 24 September 2021 findings, at times urgently requiring a detailed and fo- patients’ urinary or fecal porphyrin concentrations were cused workup with the help of the laboratory. Simple at that time. It should also be kept in mind that copropor- screening tests can lead the way, but they must always be phyrinuria is not uncommon, for example, after alcohol followed by more sophisticated analyses. Thus, the ingestion (5), and at times leads to the erroneous diagno- Watson-Schwartz test (1) for excessive amounts of uri- sis of coproporphyria. nary porphobilinogen, recently called “hoary” by this Although the authors claim that follow-up of patients Journal’s Editor (2), although still widely used in emer- under treatment for porphyria cutanea tarda can be gencies and favored for its easy execution with just a few guided by assaying plasma for uroporphyrin, one could test tubes and some reagents, must always lead to further argue that this is not necessary because clinical guidance detailed studies. A newer test, although slightly more is usually sufficient: If the skin looks good, the porphyrin complicated, is more sensitive (3). values are of very little importance. Although the clinical presentation might be confusing With their method, Hindmarsh et al. (4) confirm previ- in itself, so is the array of available laboratory studies for ous observations of an increase of plasma coproporphyrin porphyria. It should be noted that no single test covering in patients with porphyria cutanea tarda. Here, the enzy- all porphyric possibilities exists and that caution is due: If matic impasse in the biosynthetic pathway to heme is porphyria is suspected, testing for porphyrins might not ahead of coproporphyrin formation, and excessive even yield an answer because in the inducible porphyrias amounts of the latter are not to be expected. The authors (acute intermittent porphyria, variegate porphyria, and explain their finding with the assumption of an overreac- hereditary coproporphyria), assays for porphyrin precur- tion of the feedback loop in which -amino levulinic acid sors (-amino levulinic acid and porphobilinogen) are by synthase formation is excessively stimulated through a far more helpful. In fact, porphyrin studies may be deficiency of the regulatory end product, heme. This unrevealing, and thus misleading. assumption by Hindmarsh et al. (4) and others (6) has a Because the porphyrias are most often inborn errors of logical flaw because if sufficient amounts of coproporphy- metabolism and produced by enzymatic deficiencies, the rin were produced, there would be no reason for a heme ideal test would assay the specific heme biosynthetic deficiency. It seems best to abandon the term “counter- enzyme. This, however, is for technical reasons routinely regulatory compensatory enhancement” (6) in this con- available for only one porphyria, the acute intermittent text and to acknowledge that the increase of copropor- type. For the other six or seven types of porphyria, tests of phyrin concentrations in porphyria cutanea tarda remains porphyrins and their precursors are called for. These can unexplained. be performed with ease in blood and excreta, but require It would have been of interest and of potential clinical an understanding of porphyrin chemistry. If one suspects importance to attempt an adaptation of this method to porphyria as an explanation for neurologic symptoms, detect heme in plasma, in particular in the clinical setting tests for -amino levulinic acid and porphobilinogen are of treatment of a porphyric attack with hematin or heme called for. Because cutaneous manifestations of the por- arginate (7). This therapy uses bedside assessment of the phyrias are the result of excessive amounts of porphyrins, patient, supplemented by measurements of porphyrin these should be tested for. For that purpose, urinary and precursors, but measurement of the plasma concentra- blood tests are widely available. However, if a patient is tions of the therapeutically administered heme might be anuric (e.g., on dialysis), tests of feces or plasma must be of great help, for example, if peak and trough concentra- performed. For the latter, a new version is reported by tions were readily available to adjust the dose. Hindmarsh et al. (4) in this issue of the Journal. The Another clinical problem in which this method could be methodology seems sound, but the required equipment, of help is in transfused neonates with transient porphy- although not unique, reserves the procedure for highly rinemia (8), but the methodology might need to be specialized laboratories and makes it unlikely that com- adjusted because the withdrawal of ;5 mL of blood, as munity hospitals would introduce this method, helpful as required for this method, might be quite large for a it might be. newborn. Hindmarsh et al. (4) see a unique indication for their Thus, the new method to assay plasma for porphyrins method in analyzing plasma from patients with renal is appealing, but, as Hindmarsh et al. (4) acknowledge, its 932 Clinical Chemistry 45, No. 7, 1999 Clinical Chemistry 45, No. 7, 1999 933 use seems limited to a few very specific questions to be 8. Paller AS, Eramo LR, Farrell EE, Millard DD, Honig PJ, Cunningham BB. Purpuric phototherapy-induced eruption in transfused neonates: relation to answered with the help of highly specialized laboratories. transient porphyrinemia. Pediatrics 1997;100:360–4. References Claus A. Pierach 1. Pierach CA, Cardinal R, Bossenmaier I, Watson CJ. Comparison of the Hoesch and the Watson-Schwartz tests for urinary porphobilinogen. Clin Chem 1977;23:1666–8. Cecil Watson Laboratory 2. Editor’s Note to Buttery JE. Is the Watson-Schwartz screening method for porphobilinogen reliable? [Letter]. Clin Chem 1995;41:1670–1. University of Minnesota 3. Buttery JE, Chamberlain BR, Beng CG. A sensitive method of screening for and urinary porphobilinogen. Clin Chem 1989;35:2311–2. 4. Hindmarsh JT, Oliveras L, Greenway DC. Plasma porphyrins in the porphy- Abbott Northwestern Hospital rias. Clin Chem 1999;45:1070–6. Minneapolis, MN 55407-3799 5. Sutherland D, Watson CJ. Studies of coproporphyrin. VI. The effect of alcohol on the per diem excretion and isomer distribution of the urinary copropor- Downloaded from https://academic.oup.com/clinchem/article/45/7/932/5643254 by guest on 24 September 2021 phyrins. J Lab Clin Med 1951;37:29–39. 6. Jacob K, Doss MO. Excretion pattern of fecal coproporphyrin isomers I-IV in Address correspondence to: Abbott Northwestern Hospital, human porphyrias. Eur J Clin Chem Clin Biochem 1995;33:893–901. 800 East 28th St., Minneapolis, MN 55407-3799. Fax 612-863-4144; 7. Tenhunen R, Mustajoki P. Acute porphyria: treatment with heme. Semin Liver e-mail [email protected]. Dis 1998;18:53–5..