Dual gene defects involving δ-aminolaevulinate dehydratase and coproporphyrinogen oxidase in a porphyria patient

Reiko Akagi, Rikako Inoue, Shikibu Muranaka, Tsuyoshi Tahara, Shigeru Taketani, Karl Anderson, John D. Phillips, Shigeru Sassa

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

A Caucasian male had symptoms of acute porphyria, with increases in urinary δ-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→q1C, 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.

Original languageEnglish (US)
Pages (from-to)237-243
Number of pages7
JournalBritish Journal of Haematology
Volume132
Issue number2
DOIs
StatePublished - Jan 2006

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Coproporphyrinogen Oxidase
Hydro-Lyases
Porphyrias
Porphobilinogen
Aminolevulinic Acid
Genes
Sequence Analysis
Hereditary Coproporphyria
Complementary DNA
Erythrocytes
Coproporphyrins
Porphobilinogen Synthase
Acute Intermittent Porphyria
Amino Acids
Siblings
Nucleotides
Parents
Mothers
Escherichia coli
Mutation

Keywords

  • δ-aminolaevulinate dehydratase
  • Coproporphyrinogen oxidase
  • Hepatic porphyria

ASJC Scopus subject areas

  • Hematology

Cite this

Dual gene defects involving δ-aminolaevulinate dehydratase and coproporphyrinogen oxidase in a porphyria patient. / Akagi, Reiko; Inoue, Rikako; Muranaka, Shikibu; Tahara, Tsuyoshi; Taketani, Shigeru; Anderson, Karl; Phillips, John D.; Sassa, Shigeru.

In: British Journal of Haematology, Vol. 132, No. 2, 01.2006, p. 237-243.

Research output: Contribution to journalArticle

Akagi, Reiko ; Inoue, Rikako ; Muranaka, Shikibu ; Tahara, Tsuyoshi ; Taketani, Shigeru ; Anderson, Karl ; Phillips, John D. ; Sassa, Shigeru. / Dual gene defects involving δ-aminolaevulinate dehydratase and coproporphyrinogen oxidase in a porphyria patient. In: British Journal of Haematology. 2006 ; Vol. 132, No. 2. pp. 237-243.
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