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Acute Hepatic Porphyrias: Review and Recent Progress

The acute hepatic porphyrias (AHPs) are a group of four inherited diseases of heme biosynthesis that present with episodic, acute neurovisceral symptoms. The four types are 5‐aminolevulinic acid (ALA) dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and vari...

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Autores principales: Wang, Bruce, Rudnick, Sean, Cengia, Brent, Bonkovsky, Herbert L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357830/
https://www.ncbi.nlm.nih.gov/pubmed/30766957
http://dx.doi.org/10.1002/hep4.1297
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author Wang, Bruce
Rudnick, Sean
Cengia, Brent
Bonkovsky, Herbert L.
author_facet Wang, Bruce
Rudnick, Sean
Cengia, Brent
Bonkovsky, Herbert L.
author_sort Wang, Bruce
collection PubMed
description The acute hepatic porphyrias (AHPs) are a group of four inherited diseases of heme biosynthesis that present with episodic, acute neurovisceral symptoms. The four types are 5‐aminolevulinic acid (ALA) dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria. Their diagnoses are often missed or delayed because the clinical symptoms mimic other more common disorders. Recent results indicate that acute intermittent porphyria, the most severe of the more common types of AHP, is more prevalent than previously thought, occurring in about 1 in 1600 Caucasians, but with low clinical penetrance (approximately 2%‐3%). Here we provide an updated review of relevant literature and discuss recent and emerging advances in treatment of these disorders. Symptomatic attacks occur primarily in females between 14 and 45 years of age. AHP is diagnosed by finding significantly elevated levels of porphyrin precursors ALA and porphobilinogen in urine. Acute attacks should be treated promptly with intravenous heme therapy to avoid the development of potentially irreversible neurologic sequelae. All patients should be counseled about avoiding potential triggers for acute attacks and monitored regularly for the development of long‐term complications. Their first‐degree relatives should undergo targeted gene testing. Patients who suffer recurrent acute attacks can be particularly challenging to manage. Approximately 20% of patients with recurrent symptoms develop chronic and ongoing pain and other symptoms. We discuss newer treatment options in development, including small interfering RNA, to down‐regulate ALA synthase‐1 and/or wild‐type messenger RNA of defective genes delivered selectively to hepatocytes for these patients. We expect that the newer treatments will diminish and perhaps obviate the need for liver transplantation as treatment of these inborn metabolic disorders.
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spelling pubmed-63578302019-02-14 Acute Hepatic Porphyrias: Review and Recent Progress Wang, Bruce Rudnick, Sean Cengia, Brent Bonkovsky, Herbert L. Hepatol Commun Reviews The acute hepatic porphyrias (AHPs) are a group of four inherited diseases of heme biosynthesis that present with episodic, acute neurovisceral symptoms. The four types are 5‐aminolevulinic acid (ALA) dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria. Their diagnoses are often missed or delayed because the clinical symptoms mimic other more common disorders. Recent results indicate that acute intermittent porphyria, the most severe of the more common types of AHP, is more prevalent than previously thought, occurring in about 1 in 1600 Caucasians, but with low clinical penetrance (approximately 2%‐3%). Here we provide an updated review of relevant literature and discuss recent and emerging advances in treatment of these disorders. Symptomatic attacks occur primarily in females between 14 and 45 years of age. AHP is diagnosed by finding significantly elevated levels of porphyrin precursors ALA and porphobilinogen in urine. Acute attacks should be treated promptly with intravenous heme therapy to avoid the development of potentially irreversible neurologic sequelae. All patients should be counseled about avoiding potential triggers for acute attacks and monitored regularly for the development of long‐term complications. Their first‐degree relatives should undergo targeted gene testing. Patients who suffer recurrent acute attacks can be particularly challenging to manage. Approximately 20% of patients with recurrent symptoms develop chronic and ongoing pain and other symptoms. We discuss newer treatment options in development, including small interfering RNA, to down‐regulate ALA synthase‐1 and/or wild‐type messenger RNA of defective genes delivered selectively to hepatocytes for these patients. We expect that the newer treatments will diminish and perhaps obviate the need for liver transplantation as treatment of these inborn metabolic disorders. John Wiley and Sons Inc. 2018-12-20 /pmc/articles/PMC6357830/ /pubmed/30766957 http://dx.doi.org/10.1002/hep4.1297 Text en © 2018 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Reviews
Wang, Bruce
Rudnick, Sean
Cengia, Brent
Bonkovsky, Herbert L.
Acute Hepatic Porphyrias: Review and Recent Progress
title Acute Hepatic Porphyrias: Review and Recent Progress
title_full Acute Hepatic Porphyrias: Review and Recent Progress
title_fullStr Acute Hepatic Porphyrias: Review and Recent Progress
title_full_unstemmed Acute Hepatic Porphyrias: Review and Recent Progress
title_short Acute Hepatic Porphyrias: Review and Recent Progress
title_sort acute hepatic porphyrias: review and recent progress
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357830/
https://www.ncbi.nlm.nih.gov/pubmed/30766957
http://dx.doi.org/10.1002/hep4.1297
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