Relation between uroporphyrin excretion, acute attacks of hereditary coproporphyria and successful treatment with haem arginate.
1. The increased urinary excretion of porphyrins as well as of their precursors was studied in a patient with hereditary coproporphyria during two acute attacks in which symptoms differed markedly in character and severity. 2. The increase in urinary coproporphyrin was similar in the 'mild' and in the 'severe' attack, indicating a lack of correlation between coproporphyrin level and clinical symptoms. 3. Aminolaevulinic acid, porphobilinogen and uroporphyrin exhibited significantly higher values during the 'severe' attack than during the 'mild' attack. During the severe attack these three compounds were increased 18-, 14- and 46-fold, respectively, compared with increases of 3-, 3- and 8-fold, respectively, during the mild attack. 4. The striking rise in the formation of uroporphyrin was reflected in the plasma porphyrin profile, which revealed predominance of uroporphyrin. In accordance with this finding, an increase in erythrocyte porphobilinogen deaminase of 130% was recorded. 5. The fluorescence emission spectra of saline-diluted plasma (excitation of 405 nm) showed a distinct peak at 618 nm during the 'severe' episode and a small peak during the 'mild' attack, pointing to the possibility of diagnosing an attack simply by following the fluorometric screen of plasma. 6. The 'severe' attack of coproporphyria was treated with daily infusions of haem arginate, 3 mg/kg, every day for 4 days, at the end of which period a dramatic clinical response was observed. The relief of symptoms was found to be clearly related to the moderate decrease in uroporphyrin excretion observed rather than to the steep decline in the precursors.
Schoenfeld
N
N
Laboratory of Biochemical Pharmacology, Beilinson Medical Center, Petah Tikva, Israel.
Mamet
R
R
Dotan
I
I
Sztern
M
M
Levo
Y
Y
Aderka
D
D
D000208:Acute Disease; D000328:Adult; D001120:Arginine / Q000627:therapeutic use*; D004912:Erythrocytes / Q000201:enzymology; D006418:Heme / Q000627:therapeutic use*; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000097:blood; D008297:Male; D017094:Porphyrias, Hepatic / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D011166:Porphyrins / Q000097:blood; D013050:Spectrometry, Fluorescence; D014578:Uroporphyrins / Q000652:urine*
D011166:Porphyrins; D014578:Uroporphyrins; D006418:Heme; D001120:Arginine; D011163:Hydroxymethylbilane Synthase; C048849:heme arginate