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… Expand
Molecular analysis of delta-aminolevulinate dehydratase deficiency in a patient with an unusual late-onset porphyria.
TLDR
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Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria.
TLDR
The separate point mutations in each ALAD allele, as well as the altered properties of the two enzymic proteins encoded by the mutant genes in a patient with ADP, are defined. Expand
delta-Aminolevulinate dehydratase deficient porphyria: identification of the molecular lesions in a severely affected homozygote.
TLDR
Both missense mutations resulted in the synthesis of enzyme subunits such that the activity of the homooctameric enzyme was markedly reduced, thereby causing the severe infantile-onset phenotype in the affected homozygote. Expand
A novel mutation of δ‐aminolaevulinate dehydratase in a healthy child with 12% erythrocyte enzyme activity
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 probandExpand
Message amplification phenotyping of an inherited delta-aminolevulinate dehydratase deficiency in a family with acute hepatic porphyria.
TLDR
The molecular basis of the enzymatic defect responsible for acute hepatic porphyria due to delta-aminolevulinate dehydratase (ALAD) deficiency was investigated in a family including a proband with the acute disease, and the first mutation to be recognized in the human ALAD gene was recognized. Expand
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TLDR
Incubation of erythrocyte lysates with ALA decreased porphyrin formation, whereas incubation with porphobilinogen produced p Morphyrin concentrations within reference values in both patients, confirming that ALAD activity is rate-limiting in these cells. Expand
Human delta-aminolevulinate dehydratase (ALAD) gene: structure and alternative splicing of the erythroid and housekeeping mRNAs.
TLDR
Genomic clones containing human delta-aminolevulinate dehydratase (ALAD), the second enzyme in the heme pathway, were isolated and the entire sequence was determined in both orientations, finding an inverted repeat that may have resulted from gene conversion. Expand
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Abstract. Activities of δ‐aminolevulinic acid (ALA) dehydratase and porphobilinogen (PBG) deaminase, and haem content were determined in EB‐virus transformed lymphocytes from two patients withExpand
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TLDR
Two cDNAs encoding human delta-aminolevulinate dehydratase (ALA-D) were identified, recloned into bacteriophage M13, and sequenced by primer extension, finding a cysteine- and histidine-rich binding site for zinc and an unusual region of charge complementarity surrounding the active lysine residue in the catalytic site. Expand
Biochemical Diagnosis of an Hereditary Aminolaevulinate Dehydratase Deflciency in a 63-Year-Old Man
TLDR
Porphyrin metabolism was investigated in a 63-year-old male patient who developed a subacute onset polyneuropathy with predominance of motor signs in the upper limb, which revealed the existence of several heterozygous members in this family. Expand
Aminolaevulinate Dehydratase Porphyria in Infancy. A Clinical and Biochemical Study
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TLDR
Homozygous deficiency of aminolaevulinate dehydratase (porphobilinogen synthase, EC 4.2.1.24) was diagnosed in a small child with recurrent attacks of pain, vomiting, hyponatraemia and symptoms of polyneuropathy engaging motor functions including respiration. Expand
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