title: Hereditary coproporphyria: comparison of molecular and biochemical investigations in a large family.
abstract: Hereditary coproporphyria (HCP) is the least common of the three autosomal dominant acute porphyrias. To compare the sensitivity of metabolite measurements for the identification of asymptomatic HCP, we carried out a molecular and biochemical investigation of a large family in which HCP is caused by a previously unreported frameshift mutation (c.119delA). Thirteen of 19 asymptomatic family members, aged 10-72 years, were shown by mutational analysis to have HCP. The faecal coproporphyrin isomer III:I ratio was increased in all of these 13 family members; faecal total porphyrin concentration and urinary porphyrin excretion were increased in 11 and 8 of them, respectively. Plasma porphyrin concentrations were marginally increased in three individuals and plasma fluorescence emission scanning showed a porphyrin peak at 618 nm in two of these. Our results add to the evidence that an increased faecal porphyrin coproporphyrin III:I ratio is a highly sensitive test for the detection of clinically latent HCP in individuals over the age of 10 years; its sensitivity below this age remains uncertain. They also show that plasma fluorescence emission scanning is not useful for the investigation of families with HCP.
authors.affiliation: Department of Clinical Biochemistry, Leeds Teaching Hospitals, Leeds, UK. keith.allen@leedsth.nhs.uk
authors.forename: K R
authors.initials: KR
authors.lastname: Allen
authors.forename: S D
authors.initials: SD
authors.lastname: Whatley
authors.forename: T J
authors.initials: TJ
authors.lastname: Degg
authors.forename: J H
authors.initials: JH
authors.lastname: Barth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D046349:Coproporphyria, Hereditary / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005243:Feces; D005260:Female; D016368:Frameshift Mutation; D006418:Heme / Q000737:chemistry; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011166:Porphyrins / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D011166:Porphyrins; D006418:Heme