Investigations on the formation of urinary coproporphyrin isomers I-IV in 5-aminolevulinic acid dehydratase deficiency porphyria, acute lead intoxication and after oral 5-aminolevulinic acid loading

Objectives: Investigation of the metabolism of the four urinary coproporphy rin isomers I-IV in the extremely rare 5-aminolevulinic acid dehydratase (A LAD) deficiency porphyria (syn.: Doss porphyria), in acute lead intoxicatio n, and after oral 5-aminolevulinic acid (ALA) loading. Design and methods: We analyzed the excretion of total urinary coproporphyr ins and the composition of the respective isomers I-IV with ion-pair HPLC m ethods in these conditions. Results: The concentration of total coproporphyrins was about 30-fold incre ased in patients with ALAD deficiency porphyria and acute lead intoxication as compared with controls. In addition, the proportion of coproporphyrin I II as well as that of the atypical isomers II and IV were significantly ele vated at the expense of isomer I. After oral ALA administration to normal v olunteers, a 10- to 15-fold increase in the maximal concentration of total urinary coproporphyrins was observed within 12 to 24 h. Urinary levels were back to normal after another 24 h. The excretion pattern of the individual urinary coproporphyrin isomers I-IV after ALA ingestion revealed a dynamic process: initially isomer III was preferentially formed, followed by a 3-f old increase of isomers II and IV via non-enzymatic rearrangement of isomer III, and finally normalization of all four isomers occurred within 48 h. Conclusions: These results demonstrate that oral ALA loading can be used as an in vivo model to study the metabolism of the four urinary coproporphyri n isomers I-IV especially in ALAD deficiency porphyria and in acute lead po isoning. Copyright (C) 1999 The Canadian Society of Clinical Chemists.