The relative proportions of the four coproporphyrin isomers I-IV were analysed in faeces of 20 healthy subjects and 60 patients suffering from one of the seven common types of hepatic or erythropoietic hereditary
porphyrias. A newly developed, reliable method for sample preparation was applied, using reversed-phase thin layer chromatography for the isolation of naturally occurring coproporphyrin free
carboxylic acids. Accurate separation and quantitation of the individual isomers I-IV were achieved with the help of ion-pair high-performance liquid chromatography. The four coproporphyrin isomers I-IV were positively identified by on-line scanning of their fluorescence spectra in the emission and excitation modes. Recovery rates with this new analytical procedure were between 90 and 100%, and coefficients of variation varied between 0.8 and 5.7% (N = 7). Diagnostically important findings were greatly increased proportions of isomer I and decreased proportions of isomers III, II and IV in
erythropoietic porphyrias, such as
congenital erythropoietic porphyria and protoporphyria. Significantly increased proportions of isomers III, II and IV, on the other hand, were observed in acute
hepatic porphyrias, e.g.
acute intermittent porphyria and
porphobilinogen synthase deficiency porphyria, as compared with
porphyria cutanea tarda (p < 0.005 and p < 0.03, respectively). Inversion of the faecal
coproporphyrin III to I ratios and markedly elevated percentages of the atypical isomers II and IV were important diagnostic markers for
variegate porphyria and
hereditary coproporphyria. The highest proportions of isomer III were found in
hereditary coproporphyria, where the amount of the isomers II and IV exceeded that of isomer I. Asymptomatic carriers of the relevant gene defect in families with
hereditary coproporphyria could be detected by an increased faecal
coproporphyrin III to I ratio. Our results clearly demonstrate the potential of faecal
coproporphyrin I-IV isomer ratios for the diagnosis and differential diagnosis of hereditary
porphyrias.