Hereditary hepatic porphyria due to homozygous δ‐aminolevulinic acid dehydratase deficiency: studies in lymphocytes and erythrocytes

Sassa, Shigeru; Fujita, Hideaki; Doss, M.; Hassoun, A.; Verstraeten, L.; Mercelis, R.; Kappas, Attallah

doi:10.1111/j.1365-2362.1991.tb01817.x

Cited by 17 publications

(11 citation statements)

References 21 publications

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“…The patient had ALAD activity less than 3% of normal controls, both in erythrocytes (8) and in lymphocytes (9). Immunochemical studies showed that the proband's cells contained 20% positive crossreactive immunological material (CRIM) (25), suggesting the existence of a structurally altered enzyme(s).…”

Section: Resultsmentioning

confidence: 91%

“…Isolation oflymphocytes, transformation ofcells with EBV, and cultivation of lymphoblastoid cells were carried out, as described previously (9). Synthesis ofALAD cDNA.…”

Section: Methodsmentioning

confidence: 99%

“…chemicals, e.g., lead (5), succinylacetone (6,7), as well as by an inherited ALAD deficiency (8,9), which may result in the development of a clinically severe hepatic porphyria (3,4). Four unrelated cases ofinherited ALAD porphyria (ADP) have been reported to date (9).…”

mentioning

confidence: 99%

“…Four unrelated cases ofinherited ALAD porphyria (ADP) have been reported to date (9). In our previous study (10), we described a molecular defect in an ALAD allele, termed 'G2', in an adultonset proband with ADP, originally reported from Germany (8).…”

mentioning

confidence: 99%

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Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria.

Ishida¹,

Fujita²,

Fukuda³

et al. 1992

J. Clin. Invest.

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Cloning and expression of the defective genes for b-aminolevulinate dehydratase (ALAD) from a patient with inherited ALAD deficiency porphyria (ADP) were carried out. Cloning of cDNAs for the defective ALAD were performed from EBVtransformed lymphoblastoid cells of the proband, and nucleotide sequences were determined. Two separate point mutations resulting in a single amino acid change in each ALAD allele were identified. One, C718 -* T, termed 'Gl', occurred in the allele within the substrate-binding site, producing an Arge4 --Trp substitution; the other, G'0' --A, termed 'G2', occurred downstream of this site in the other allele, resulting in an Ala'4 Thr substitution. Using the reverse transcription-polymerase chain reaction, the mother, the brother, and the sister were shown to have the Gi defect. Expression of the G1 cDNA in Chinese hamster ovary cells produced ALAD protein with little activity; the G2 cDNA produced the enzyme with 50% normal activity. Pulse-labeling studies demonstrated that the G1 enzyme had a normal half life, while the G2 enzyme had a markedly decreased half life. These data thus define 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. (J.

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Section: Resultsmentioning

confidence: 91%

“…Isolation oflymphocytes, transformation ofcells with EBV, and cultivation of lymphoblastoid cells were carried out, as described previously (9). Synthesis ofALAD cDNA.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria.

Ishida¹,

Fujita²,

Fukuda³

et al. 1992

J. Clin. Invest.

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“…Isolation of lymphocytes and transformation with Epstein-Barr virus were carried out as described previously (15).…”

mentioning

confidence: 99%

The molecular defect of ferrochelatase in a patient with erythropoietic protoporphyria.

Nakahashi¹,

Fujita²,

Taketani³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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The molecular basis of an inherited defect of ferrochelatase in a patient with erythropoietic protoporphyria (EPP) was investigated. Ferrochelatase is the terminal enzyme in the heme biosynthetic pathway and catalyzes the insertion of ferrous iron into protoporphyrin IX to form heme. In EpsteinBarr virus-transformed lymphoblastoid cells from a proband with EPP, enzyme activity, an immunochemically quantifiable protein, and mRNA content of ferrochelatase were about one-half the normal level. In contrast, the rate of ftrnription of ferrochelatase mRNA in the proband's cells was normal, suggesting that decreased ferrochelatase mRNA is due to an unstable transcript. cDNA clones encoding ferrochelatase in the proband, isolated by amplification using the polymerase chain reaction, were found to be classifid either into those encoding the normal protein or into those encoding an abnormal protein that lacked exon 2 of the ferrochelatase gene, indicating that the proband is heterozygous for the ferrochelatase defect. Genomic DNA analysis revealed that the abnormal allele had a point mutation, C -* T, near the acceptor site of intron 1. This point mutation appears to be responsible for the post-transcriptional splicing abnormality resulting in an aberrant transcript of ferrochelatase in this patient.

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Clinical Remission of Delta‐Aminolevulinic Acid Dehydratase Deficiency Through Suppression of Erythroid Heme Synthesis

et al. 2019

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Hereditary hepatic porphyria due to homozygous δ‐aminolevulinic acid dehydratase deficiency: studies in lymphocytes and erythrocytes

Cited by 17 publications

References 21 publications

Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria.

Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria.

The molecular defect of ferrochelatase in a patient with erythropoietic protoporphyria.

Clinical Remission of Delta‐Aminolevulinic Acid Dehydratase Deficiency Through Suppression of Erythroid Heme Synthesis

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