Acute Intermittent Porphyria

Abstract

THE TERM porphobilinogen (PBG) was introduced by Waldenstr\l=o"\mand Vahlquist 1 to designate the Ehrlich aldehyde-reacting chromogen which Sachs 2 first distinguished from urobilinogen and which characterizes the urine in cases of acute porphyria. The dominantly genetic character of acute intermittent porphyria, as well as its ease of confusion with many other diseases, the protection that may be offered by knowledge of precipitating factors, such as barbiturates, together with newer knowledge about therapy during relapse, emphasize the need of definitive diagnosis.Historical Background PBG was first crystallized by Westall3 and its monopyrrolic structure was soon elucidated by Cookson and Rimington.4 Subsequent studies have shown that it is an intermediary in heme biosynthesis, although not in evidence under normal circumstances and only rarely in diseases other than porphyria.In 1941 Watson and Schwartz 5 observed that the Ehrlich aldehyde compound of PBG is not extracted by chloroform, in contradistinction to that of urobilinogen, and pointed out that this difference was characteristic of urine samples from patients with acute porphyria. Hammond and Welcker 6 examined 1,000 samples from as many general hospital cases of all varieties and found no positive reactions by this simple method. This gave some indication of the relative infrequence of the reaction in diseases other than acute porphyria. Nevertheless, false-positive tests are at times observed and have given rise to incorrect diagnoses. Positive tests were reported by one of us (C. J. W.) in several cases of severe systemic disease in which there was nothing suggestive of acute porphyria,7 including Hodgkin's disease, hepatic cirrhosis, poliomyelitis, tetanus, cancer of the pancreas, carcinomatosis of the bone marrow, and intra-abdominal hemorrhage, as from a dissecting aneurysm.At the time these cases were studied, the nature of the Ehrlich reactor was not examined by additional methods such as will be discussed; hence, it is not certain that porphobilinogen itself was represented. Schwartz8a observed that the porphobilinogen aldehyde compound is not extracted by butanol, in contrast to certain other Ehrlich reactors not extracted by chloroform. This behavior has been observed both in human and experimental porphyria. Schwartz and co-workers8bl 8c found that in the urine of rabbits in the early stages of experimental porphyria, a substance yielding a butanol-soluble Ehrlich compound was often preponderant and later gave way to PBG itself. Normal rabbit urine at times contains a similar substance in small amounts. A similar Ehrlich reactor was observed, without PBG, in a patient with porphyria who developed volvulus of the cecum.9 The chromogen itself was extractible by ethyl acetate at pH 4.0 (acetic), quite unlike PBG. This behavior has also been well correlated in other instances in which butanol solubility of the aldehyde compound has been noted. There is reason to believe that a variety of substances, some as yet unidentified, may behave in this ...

A high urinary urobilinogen/serum total bilirubin ratio indicates acute hepatic porphyria in patients with abdominal pain

“…Both PBG and urobilinogen can react with Ehrlich's reagent and form a red condensation product in the first step of Watson–Schwartz test 22 . As such, in the second step of the test, chloroform is added to the solution to distinguish the PBG-Ehrlich compound from the urobilinogen-Ehrlich complex.…”

A High Urinary Urobilinogen / Serum Total Bilirubin Ratio Reported in Abdominal Pain Patients Can Indicate Acute Hepatic Porphyria

“…Urobilinogen, a substance being routinely examined in urinalysis, can also react with Ehrlich's reagent and form a red product 23 . As such, in the second step of Watson-Schwartz test, chloroform is added to the solution to distinguish the PBG-Ehrlich compound from the urobilinogen-Ehrlich complex.…”

Acute Hepatic Porphyria

“…The need for a rapid PBG test was recognized in the 1940's, and qualitative assays using Ehrlich's reagent were developed for ED staff. 39 – 41 With implementation of the U.S. Clinical Laboratory Improvement Amendments (CLIA) in 1992, however, the rapid tests were deemed moderately complex, and their use was restricted to trained laboratory personnel. The CLIA legislation coincided with the rise of large commercial laboratories, which could offer specialty tests, such as those for porphyria, at a cost well below that of an individual hospital.…”