A 27-year-old woman who had recurrent
pain in renal bed since 1998 with increasing character, was stationary admitted. The patient showed dark urine, complained of
hair loss and took since 1994 a
hormonal oral contraceptive. No photosensitivity was observed. Determinations of urinary
porphyrin metabolites in 1998 revealed a
porphyria cutanea tarda like excretion pattern with elevations of uro- (1767 nmol/24 hr, normal <29 nmol/24 hr) and heptacarboxyporphyrin (568 nmol/24 hr; normal <4 nmol/24 hr). Follow-up studies in feces showed the characteristics of a
hereditary coproporphyria with dominance of coproporphyrin isomer III (total= 1470 nmol/g, isomer III= 93%), (normal: <37 nmol/g, isomer III = 25-35%). The excretion of
porphyrin precursors (
delta-aminolevulinic acid and
porphobilinogen) was increased by taking an ethinylestradiol-cyproteronacetate-preparation, but acute and/or chronic manifestations were not observed.
Coproporphyrinogen oxidase activity was decreased to 35% in the patient (normal=138+/-21 pkat/
g protein; x+/-s), whereas the activity of red cell
uroporphyrinogen decarboxylase was normal. Her mother and both sisters could be verified as heterozygous gene carriers of
hereditary coproporphyria by their urinary and fecal excretion parameters and because of reduced
coproporphyrinogen oxidase activity up to 50%. The father was normal with respect to his genotype. Molecular analysis revealed a hitherto unknown mutation with the transversion of a
cytosine to
thymine at
nucleotide position 854 in exon 4 of the
coproporphyrinogen oxidase gene. The gene defect was confirmed by DGGE in the mother and her three daughters. The investigation of the immunological nature of the defective
coproporphyrinogen oxidase gene from the whole family revealed decreased concentrations of
coproporphyrinogen oxidase protein in the patient, her mother and her two sisters.