δ-Aminolevulinate dehydratase (ALAD) porphyria

The first case in North America with two novel ALAD mutations

Reiko Akagi, Noriko Kato, Rikako Inoue, Karl Anderson, Eileen K. Jaffe, Shigeru Sassa

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The molecular basis of the enzymatic defect responsible for δ-aminolevulinate dehydratase (ALAD) porphyria (ADP) was investigated in a 14-year-old male who presented clinical and laboratory findings typical of ADP. Nucleotide sequence analysis of ALAD cDNAs from the proband revealed two novel mutations, a 265G to A base transition (C1) and a 394C to T base transition (C2), resulting in amino acid substitutions, Glu89Lys and Cys132Arg, respectively. Both mutations were present within exon 5 of the ALAD gene, and appeared to influence the binding of zinc to the enzyme which is essential for enzyme activity. It was found that the C1 mutation was inherited from his father, while the C2 mutation was from his mother. Expression of these mutant ALAD cDNAs in Chinese hamster ovary cells produced normal ALAD mRNA levels, but markedly decreased ALAD protein and enzyme activity. These results suggest that the combination of the two aberrant ALADs with little enzyme activity accounts for the markedly decreased ALAD activity observed in the proband. This case represents the molecular analysis of the ALAD gene defects in the first case of ADP identified in North America, who is a compound heterozygote for two novel ALAD gene defects.

Original languageEnglish (US)
Pages (from-to)329-336
Number of pages8
JournalMolecular Genetics and Metabolism
Volume87
Issue number4
DOIs
StatePublished - Apr 2006

Fingerprint

Hydro-Lyases
Porphyrias
North America
Mutation
Enzyme activity
Genes
Enzymes
Defects
Complementary DNA
Aminolevulinic Acid
Amino Acid Substitution
Heterozygote
Cricetulus
Fathers
Sequence Analysis
Zinc
Ovary
Exons
Substitution reactions
Nucleotides

Keywords

  • δ-Aminolevulinate dehydratase
  • Compound heterozygote
  • Doss porphyria
  • Hepatic porphyria
  • Point mutation

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

Cite this

δ-Aminolevulinate dehydratase (ALAD) porphyria : The first case in North America with two novel ALAD mutations. / Akagi, Reiko; Kato, Noriko; Inoue, Rikako; Anderson, Karl; Jaffe, Eileen K.; Sassa, Shigeru.

In: Molecular Genetics and Metabolism, Vol. 87, No. 4, 04.2006, p. 329-336.

Research output: Contribution to journalArticle

Akagi, Reiko ; Kato, Noriko ; Inoue, Rikako ; Anderson, Karl ; Jaffe, Eileen K. ; Sassa, Shigeru. / δ-Aminolevulinate dehydratase (ALAD) porphyria : The first case in North America with two novel ALAD mutations. In: Molecular Genetics and Metabolism. 2006 ; Vol. 87, No. 4. pp. 329-336.
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