Summary A Caucasian male had symptoms of
acute porphyria, with increases in urinary delta-aminolaevulinic
acid (ALA),
porphobilinogen (PBG) and coproporphyrin that were consistent with
hereditary coproporphyria (HCP). However, a greater than expected increase in ALA, compared with PBG, and a substantial increase in erythrocyte
zinc protoporphyrin, suggested additional ALA
dehydratase (
ALAD) deficiency. Nucleotide sequence analysis of
coproporphyrinogen oxidase (CPO)
cDNA of the patient, but not of the parents, revealed a novel
nucleotide transition G835-->C, resulting in an
amino acid change, G279R. The mutant CPO
protein expressed in Escherichia coli was unstable, and produced about 5% of activity compared with the wild-type CPO. Erythrocyte ALAD activity was 32% of normal in the proband. Nucleotide sequence analysis of cloned ALAD cDNAs from the patient revealed a C36-->G base transition (F12L
amino acid change). The F12L ALAD mutation, which was found in the mother and a brother, was previously described, and is known to lack any
enzyme activity. This patient thus represents the first case of
porphyria where both CPO and ALAD deficiencies were demonstrated at the molecular level.