δ-Aminolevulinate dehydratase (ALAD) porphyria: The first case in North America with two novel ALAD mutations

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

doi:10.1016/j.ymgme.2005.10.011

Cited by 45 publications

(37 citation statements)

References 27 publications

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“…ADP, an autosomal recessive disease resulting from deficiency of ALA dehydratase enzyme, is the least common porphyria, with only 6 cases described with confirmed genetic or molecular defect . LT was performed for a 7‐year‐old boy with ADP who had severe frequent acute porphyria attacks.…”

Section: Lt In Hepatic Porphryiamentioning

confidence: 99%

Liver transplantation in the management of porphyria

Singal

Parker

Bowden³

et al. 2014

Hepatology

115

122

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Porphyrias are a group of eight metabolic disorders, each resulting from a mutation that affects an enzyme of the heme biosynthetic pathway. Porphyrias are classified as hepatic or erythropoietic, depending upon the site where the gene defect is predominantly expressed. Clinical phenotypes are classified as follows: (1) acute porphyrias with neurovisceral symptoms: acute intermittent porphyria; delta amino-levulinic acid hydratase deficiency porphyria; hereditary coproporphyria; and variegate porphyria and (2) cutaneous porphyrias with skin blistering and photosensitivity: porphyria cutanea tarda; congenital erythropoietic porphyria; hepatoerythropoietic porphyria and both erythropoietic protoporphyrias: autosomal dominant and X-linked. Liver transplantation (LT) may be needed for recurrent and/or life-threatening acute attack in acute intermittent porphyria or acute liver failure or end-stage chronic liver disease in erythropoietic protoporphyria. LT in acute intermittent porphyria is curative. Erythropoietic protoporphyria patients needing LT should be considered for bone marrow transplantation to achieve cure. Conclusion This article provides an overview of porphyria with diagnostic approaches and management strategies for specific porphyrias and recommendations for LT with indications, pretransplant evaluation, and posttransplant management.

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Section: Lt In Hepatic Porphryiamentioning

confidence: 99%

Liver transplantation in the management of porphyria

Singal

Parker

Bowden³

et al. 2014

Hepatology

115

122

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“…This method offers advantages over earlier more cumbersome, time-consuming, and less specific methods. In spite of some efforts, we have been unable to locate patients who had been previously diagnosed with Doss porphyria 19. It is hoped that the specific assays developed in this laboratory, together with the increasing availability of tandem mass spectrometers in clinical laboratories, will contribute to improved diagnostics of porphyrias in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Direct Assay of δ-Aminolevulinic Acid Dehydratase in Heme Biosynthesis for the Detection of Porphyrias by Tandem Mass Spectrometry

et al. 2010

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We report a new assay of human δ-aminolevulinic acid dehydratase (ALAD), an enzyme converting δ-aminolevulinic acid (ALA) into porphobilinogen. The assay is developed for use in the clinical diagnosis of δ-aminolevulinic acid dehydratase-deficient porphyria, a rare enzymatic deficiency of the heme biosynthetic pathway. The assay involves the incubation of erythrocyte lysate with the natural substrate, ALA, followed by quantitative in situ conversion of porphobilinogen to its butyramide, and liquid-liquid extraction into a mass spectrometer-friendly solvent. Quantitation of the butyrylated porphobilinogen is done by electrospray ionization tandem mass spectrometry, using a deuterium labeled internal standard. The assay stays well within the range wherein ALAD activity is linear with time. The Km of ALAD for ALA was measured as 333 μM, and the Vmax was 19.3 μM/hr. Average enzyme activity among a random sample of 36 anonymous individuals was 277 μmol/L erythrocyte lysate/hour with a standard deviation of 90 μmol/L erythrocyte lysate/hour. The tandem mass spectrometric assay should easily detect the enzyme deficiency, which causes a reduction of activity by 95–99%. The assay shows good reproducibility, low background, requires a simple workup, and uses a commercially available substrate.

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“…Skin lesions do not occur in AIP except with concurrent severe renal insufficiency. 77 ADP is very rare and less understood, with only six documented cases in the literature, all of whom were males, 78 including a child with especially severe manifestions. 79…”

Section: Acute Porphyriasmentioning

confidence: 99%

“…Only six cases, all of whom were unrelated males, have been documented in the literature. 78 Along with the other three acute porphyrias, ADP is often classified as hepatic. However, the site of overproduction of ALA in this disease is not established, and marked elevation in erythrocyte zinc protoporphyrin levels suggests that the marrow might be an important source of excess ALA.…”

Section: E Testing For Adp and Other Causes Of Alad Deficiencymentioning

confidence: 99%