A molecular, enzymatic and clinical study in a family with hereditary coproporphyria.

A 30-year-old woman suffered from acute crises with abdominal, neurological and psychiatric complaints. Urinary haem precursors and faecal porphyrins were excessively elevated compared to the upper level of the normal range. Urinary coproporphyrin isomer III was increased and faecal coproporphyrin isomers I and III showed a complete inversion of the normal ratio. Thus, hereditary coproporphyria was diagnosed in this woman. The father, one brother and a sister were shown to be gene carriers of hereditary coproporphyria by their urinary and faecal excretory constellations. The excretory patterns of the mother and a second brother were normal. Coproporphyrinogen oxidase activity was decreased to 49% and 58%, in the patient and her father, respectively. The mother's enzyme activity was normal (98%). Coproporphyrinogen oxidase concentration was enhanced 1.8-fold and 2.7-fold in the patient and her father, respectively. Mutation analysis revealed the insertion of an adenine at position 857 in exon 4 of the coproporphyrinogen oxidase gene. The gene defect was confirmed by denaturing gradient gel electrophoresis in the patient and her father. The patient was treated by intravenous interval therapy with haem arginate for 10 months, with good clinical and metabolic response.