A novel mutation of δ‐aminolaevulinate dehydratase in a healthy child with 12% erythrocyte enzyme activity

@article{Akagi1999ANM,
  title={A novel mutation of $\delta$‐aminolaevulinate dehydratase in a healthy child with 12\% erythrocyte enzyme activity},
  author={Reiko Akagi and Yumiko Yasui and Pauline Harper and Shigeru Sassa},
  journal={British Journal of Haematology},
  year={1999},
  volume={106}
}
Cloning, expression and phenotype studies of the defective gene for δ‐aminolaevulinate dehydratase (ALAD) in a family with an asymptomatic girl who had ALAD deficiency were carried out. The proband was identified by neonatal ALAD screening, and had erythrocyte ALAD activity at 12% of the normal control. She was heterozygous for ALAD deficiency, which was inherited from her father. Nucleotide sequence analysis of the cloned ALAD cDNA revealed C36 to G and T168 to C mutations on the same allele… 
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23 Citations

Novel molecular defects of the δ‐aminolevulinate dehydratase gene in a patient with inherited acute hepatic porphyria

Cloning and expression of the defective gene for δ‐aminolevulinate dehydratase (ALAD) from the second of 2 German patients with ALAD deficiency porphyria (ADP) demonstrate that the proband was associated with 2 novel molecular defects of the ALAD gene and account for the extremely low ALAD activity in his erythrocytes.

Molecular analysis of delta-aminolevulinate dehydratase deficiency in a patient with an unusual late-onset porphyria.

Findings indicate that while the proband was heterozygous for ALAD deficiency, the G(397) to A transition resulting in the G133R substitution is responsible for ADP, and the clinical porphyria developed presumably due to an expansion of the polycythemic clone in erythrocytes that carried the mutant alad allele.

delta-Aminolevulinate dehydratase (ALAD) porphyria: the first case in North America with two novel ALAD mutations.

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

This patient represents the first case of porphyria where both CPO and ALAD deficiencies were demonstrated at the molecular level, and a novel nucleotide transition G835→C, resulting in an amino acid change, G279R.

Highly heterogeneous nature of delta-aminolevulinate dehydratase (ALAD) deficiencies in ALAD porphyria.

This study represents the first complete analysis of 9 mutants of ALAD identified in ADP and indicates the highly heterogeneous nature of mutations in this disorder.

Co-synthesis of Human δ-Aminolevulinate Dehydratase (ALAD) Mutants with the Wild-type Enzyme in Cell-free System—Critical Importance of Conformation on Enzyme Activity—

Findings indicate that cell-free synthesis of ALAD proteins reflects enzymatic activities found in patients, and suggest that, in addition to the direct effect of mutations on the catalytic activity, conformational effects play an important role in determining enzyme activity.

ALAD porphyria is a conformational disease.

It is proposed that the disequilibrium of morphheein assemblies broadens the definition of conformational diseases beyond the prion disorders and that ALAD porphyria is the first example of a morpheein-based conformational disease.

The third case of Doss porphyria (δ-amino-levulinic acid dehydratase deficiency) in Germany

It is suggested that the observed compound heterozygosity of the ALAD gene may be responsible for Doss porphyria in the proband, which is now almost free of clinical symptoms.

5-Aminolaevulinic Acid Dehydratase, Porphobilinogen Deaminase and Uroporphyrinogen III Synthase

X-ray structures of the enzyme from humans and a thermophilic bacterium have enabled models of the catalytic process to be proposed, and current proposals involve the binding of both substrate moieties by formation of Schiff bases with two invariant active site lysine residues.

Heme biosynthesis and the porphyrias.

  • J. Phillips
  • Medicine, Biology
    Molecular genetics and metabolism
  • 2019

References

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