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

@article{Akagi2000NovelMD,
  title={Novel molecular defects of the $\delta$‐aminolevulinate dehydratase gene in a patient with inherited acute hepatic porphyria},
  author={Reiko Akagi and Ryo Shimizu and Kazumichi Furuyama and Manfred O. Doss and Shigeru Sassa},
  journal={Hepatology},
  year={2000},
  volume={31}
}
Cloning and expression of the defective gene for δ‐aminolevulinate dehydratase (ALAD) from the second of 2 German patients with ALAD deficiency porphyria (ADP), who had been originally reported by Doss et al. in 1979, were performed. Cloning of cDNAs for the defective ALAD were performed using Epstein‐Barr virus (EBV)‐transformed lymphoblastoid cells of the proband, and nucleotide sequences of cloned cDNA were determined. Two separate mutations of ALAD cDNA were identified in each ALAD allele… 

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.

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.

Survival of two patients with severe δ-aminolaevulinic acid dehydratase deficiency porphyria

Urinary excretions of δ-aminolaevulinic acid and coproporphyrin III were excessively increased in the two patients with compound-heterozygous δ -aminola Evulinic Acid dehydratase deficiency porphyria.

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.

Single Amino Acid Mutations Alter the Distribution of Human Porphobilinogen Synthase Quaternary Structure Isoforms (Morpheeins)*

The structures of human PBGS morpheeins are analyzed for key interactions that would be predicted to affect the oligomeric assembly, and the metastable nature of the R240A hexamer supports the hypothesis that octameric and hexameric morphheeins of PBGS are very close in energy.

Heme biosynthesis and the porphyrias.

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

Heme biosynthesis and the porphyrias

Porphyria cutanea tarda (PCT) is the only porphyria that has both genetic and/or environmental factors that lead to reduced activity of uroporphyrinogen decarboxylase in the liver.

SEVEN STEPS TO DIAGNOSE DELTA-AMINOLEVULINIC ACID DEFICIENCY PORPHYRIA

The case of a male patient with at least two possible causes for his symptoms, the diagnostic process and the outcome of Delta-aminolevulinic acid dehydratase porphyria is presented.

Porphyrias in Japan: Compilation of All Cases Reported through 2002

This survey revealed the difficulty of diagnosing porphyria in the absence of specific laboratory testing for por-phyrins and their precursors in urine, stool, plasma, and erythrocyte samples, and that as many as 71% of acute hepatic porphyrias cases were initially diagnosed as nonporphyria and later revised or corrected to porphyira.

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