The Pattern of Porphyrin Isomer Accumulation and Excretion in Symptomatic Porphyria

Abstract

1.Thin-layer chromatography of porphyrin methyl esters provides a useful and rapid technique for resolving mixtures of porphyrins from biological samples.2. Application of this technique to urinary, faecal and hepatic porphyrins from patients with symptomatic porphyria revealed five porphyrins of interest which could be identified by mass spectrometry as the methyl esters of porphyrins with 8-, 7-, 6-, 5-and 4-carboxyl groups. Millimolar extinction coefficients at the Soret absorption maxima for these porphyrin methyl esters in chloroform solution were measured.3. A consistent pattern of urinary porphyrin excretion in symptomatic porphyria was seen with 8-, 7-, 6-, 5-and 4-carboxyl porphyrins constituting approximately 60%, 25%, 3%, 3% and 9% of the total respectively. Uroporphyrin (73%), heptacarboxylic porphyrin (26%) and hexa-carboxylic porphyrin (I %) were the only porphyrins detected in the liver of one patient.4. Isomer analysis of excreted and hepatic porphyrins revealed that uroporphyrin was approximately 35% isomer I11 , hepta-and hexa-carboxylic porphyrins almost all isomer I11 and penta-carboxylic and coproporphyrin approximately 50% isomer 111. 5. To explain these findings it is suggested that there are two metabolic pathways for the handling of 6-aminolaevulic acid (ALA) in the liver.Symptomatic porphyria (porphyria cutanea tarda) is a well defined syndrome characterized clinically by increased mechanical fragility, blistering, pigmentation and superficial ulceration of the sun-exposed skin. A history of alcohol abuse and evidence of chronic parenchymatous liver disease can usually be elicited. The serum iron concentration is frequently raised and siderosis of the liver of varying degree is invariably present. Unlike inherited forms of hepatic porphyria, a positive family history of the disorder is exceptional and acute attacks are unknown.The disease is distinguished biochemically by a characteristic pattern of haem precursor

Environmental Chemical Exposures and Disturbances of Heme Synthesis

“…In VP, one small case series reported the lowest values of urine ALA, PBG, uroporphyrin, and coproporphyrin in acute attacks to be 9, 12, 190, and 27 times the mean control values, respectively (26), which was consistent with the higher average values reported in a larger series (27). In reports of the cutaneous porphyrias, urine uroporphyrin in PCT increased to about 10 to 375 times normal in over 300 reported cases (except in one case (59), where a single value was within normal range) (60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70), and in EPP, reported erythrocyte protoporphyrin values ranged from 2.4 to Environmental Health Perspectives * Vol 105, Supplement 1 * February 1997 90 times normal (31,65,71), with the exception of a single patient in whom it was elevated by only a factor of 1.4 (31). Finally, in reports of the less common (autosomal-recessive) cutaneous porphyrias, urine porphyrins in CEP were 20 to 60 times normal (7) (96)(97)(98).…”

Skin porphyrin and UV-A irradiation.

“…This was similar to that in human porphyria cutanea tarda as reported by Chu and Chu (1967) and Dowdle et al (1970) who mentioned predominance of Up and Hepta in the urine. In the skin, moreover, a similar observation was obtained on porphyrin distribution; the pattern was Up (55.0%)>Hepta(14.1%)> Cp (12.3%) >Hexa (1.9%).…”

Environmental chemical exposures and disturbances of heme synthesis.

“…In VP, one small case series reported the lowest values of urine ALA, PBG, uroporphyrin, and coproporphyrin in acute attacks to be 9,12,190, and 27 times the mean control values, respectively (26), which was consistent with the higher average values reported in a larger series (27). In reports of the cutaneous porphyrias, urine uroporphyrin in PCT increased to about 10 to 375 times normal in over 300 reported cases (except in one case (59), where a single value was within normal range) (60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70) (31,65,71), with the exception of a single patient in whom it was elevated by only a factor of 1.4 (31). Finally, in reports of the less common (autosomal-recessive) cutaneous porphyrias, urine porphyrins in CEP were 20 to 60 times normal (7) and in HEP, urine uroporphyrin increased by at least 20-fold and erythrocyte porphyrins increased by 5-to 10-fold (28,29,72).…”