Hereditary coproporphyria: comparison of molecular and biochemical investigations in a large family

J Inherit Metab Dis. 2005;28(5):779-85. doi: 10.1007/s10545-005-0092-z.

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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Coproporphyria, Hereditary / blood
  • Coproporphyria, Hereditary / diagnosis
  • Coproporphyria, Hereditary / genetics*
  • DNA Mutational Analysis
  • Family Health
  • Feces
  • Female
  • Frameshift Mutation
  • Heme / chemistry
  • Humans
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mutation
  • Pedigree
  • Porphyrins / metabolism
  • Sequence Analysis, DNA

Substances

  • Porphyrins
  • Heme