Coexistence of hereditary coproporphyria and porphyria cutanea tarda: a new form of dual porphyria

Abstract

Dual porphyrias are characterized by two independent disturbances of porphyrin metabolism. At first a porphyria cutanea tarda was diagnosed in a 26-year-old female with back pain and red urine. Later a hereditary coproporphyria was ascertained by additional examinations. The metabolites of porphyrin metabolism were analyzed chromatographically. The activities of coproporphyrinogen oxidase and uroporphyrinogen decarboxylase were determined in blood cells. Molecular analysis was carried out by denaturing gradient gel electrophoresis followed by direct sequencing. Excessive porphyrinuria of 3,128 nmol/24 h (normal < 165 nmol/24 h) with dominance of uro- and heptacarboxyporphyrin (75% of total porphyrins) indicated that the patient suffered from porphyria cutanea tarda. The course of the examination showed an alteration of the constellation with dominance of urinary and fecal coproporphyrin isomer III, which is characteristic for hereditary coproporphyria. Porphyrin precursors and porphyrins increased under the application of ethinylestradiol-cyproteronacetat. The dominance of coproporphyrin III stayed constant in feces besides enhanced urinary uro- and heptacarboxyporphyrin. The activity of the coproporphyrinogen oxidase was diminished to 35%. The uroporphyrinogen decarboxylase in erythrocytes was normal. The mother and both sisters were recognized as heterozygous gene carriers of hereditary coproporphyria in the latent phase by enhanced coproporphyrin with isomer I/III inversion in feces and decrease of the coproporphyrinogen oxidase activity to about 50%. Molecular analyses resulted in a point mutation at exon 4 (854C-->T), which revealed in an amino acid exchange (P258L) in the coproporphyrinogen oxidase protein. The hereditary coproporphyria is caused by a new mutation in the coproporphyrinogen oxidase gene in the case of a dual porphyria with co-existence of porphyria cutanea tarda and hereditary coproporphyria. The sporadic, hepatic porphyria cutanea tarda Type I is induced by estrogens. The large excretory variations reflect the influence of hormonal factors on the porphyria process of hereditary coproporphyria and porphyria cutanea tarda.