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Case Report: Lack of Response to Givosiran in a Case of ALAD Porphyria

Introduction: 5-Aminolevulinic acid dehydratase (ALAD) porphyria (ADP) is an autosomal recessive disease characterized by a profound deficiency in ALAD, the second enzyme in the heme biosynthetic pathway, and acute neurovisceral attacks with abdominal pain and peripheral neuropathy. Hemin infusions...

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Autores principales: Graff, Erica, Anderson, Karl E., Levy, Cynthia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386060/
https://www.ncbi.nlm.nih.gov/pubmed/35991568
http://dx.doi.org/10.3389/fgene.2022.867856
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author Graff, Erica
Anderson, Karl E.
Levy, Cynthia
author_facet Graff, Erica
Anderson, Karl E.
Levy, Cynthia
author_sort Graff, Erica
collection PubMed
description Introduction: 5-Aminolevulinic acid dehydratase (ALAD) porphyria (ADP) is an autosomal recessive disease characterized by a profound deficiency in ALAD, the second enzyme in the heme biosynthetic pathway, and acute neurovisceral attacks with abdominal pain and peripheral neuropathy. Hemin infusions are often effective in treating and preventing such attacks. Givosiran was recently approved for prevention of attacks of acute hepatic porphyrias (AHPs), including ADP, but, to our knowledge, has not yet been applied in patients with this ultrarare disease. Case Description: We update the clinical course and report new treatment outcomes of a 32-year-old man with ADP managed for many years with weekly prophylactic hemin infusions. He has developed evidence of iron overload and was more recently found to have compensated cirrhosis. The patient was started on givosiran (Givlaari™, Alnylam), a small interfering RNA (siRNA) therapeutic that is effective in preventing frequently recurring attacks of acute intermittent porphyria (AIP), the most common type of AHP. Discussion: No adverse effects of givosiran on the liver were observed in this patient with cirrhosis during 6 months of treatment with givosiran. The patient has continued to have recurrent attacks, with transient decreases in ALA levels only as related to treatment of his attacks with hemin. Our experience limited to one patient with ADP suggests that givosiran may not be effective in this type of acute porphyria. Since ADP may have an erythropoietic component, treatment with hydroxyurea, which was beneficial in one previous case, is planned.
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spelling pubmed-93860602022-08-19 Case Report: Lack of Response to Givosiran in a Case of ALAD Porphyria Graff, Erica Anderson, Karl E. Levy, Cynthia Front Genet Genetics Introduction: 5-Aminolevulinic acid dehydratase (ALAD) porphyria (ADP) is an autosomal recessive disease characterized by a profound deficiency in ALAD, the second enzyme in the heme biosynthetic pathway, and acute neurovisceral attacks with abdominal pain and peripheral neuropathy. Hemin infusions are often effective in treating and preventing such attacks. Givosiran was recently approved for prevention of attacks of acute hepatic porphyrias (AHPs), including ADP, but, to our knowledge, has not yet been applied in patients with this ultrarare disease. Case Description: We update the clinical course and report new treatment outcomes of a 32-year-old man with ADP managed for many years with weekly prophylactic hemin infusions. He has developed evidence of iron overload and was more recently found to have compensated cirrhosis. The patient was started on givosiran (Givlaari™, Alnylam), a small interfering RNA (siRNA) therapeutic that is effective in preventing frequently recurring attacks of acute intermittent porphyria (AIP), the most common type of AHP. Discussion: No adverse effects of givosiran on the liver were observed in this patient with cirrhosis during 6 months of treatment with givosiran. The patient has continued to have recurrent attacks, with transient decreases in ALA levels only as related to treatment of his attacks with hemin. Our experience limited to one patient with ADP suggests that givosiran may not be effective in this type of acute porphyria. Since ADP may have an erythropoietic component, treatment with hydroxyurea, which was beneficial in one previous case, is planned. Frontiers Media S.A. 2022-08-04 /pmc/articles/PMC9386060/ /pubmed/35991568 http://dx.doi.org/10.3389/fgene.2022.867856 Text en Copyright © 2022 Graff, Anderson and Levy. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Graff, Erica
Anderson, Karl E.
Levy, Cynthia
Case Report: Lack of Response to Givosiran in a Case of ALAD Porphyria
title Case Report: Lack of Response to Givosiran in a Case of ALAD Porphyria
title_full Case Report: Lack of Response to Givosiran in a Case of ALAD Porphyria
title_fullStr Case Report: Lack of Response to Givosiran in a Case of ALAD Porphyria
title_full_unstemmed Case Report: Lack of Response to Givosiran in a Case of ALAD Porphyria
title_short Case Report: Lack of Response to Givosiran in a Case of ALAD Porphyria
title_sort case report: lack of response to givosiran in a case of alad porphyria
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386060/
https://www.ncbi.nlm.nih.gov/pubmed/35991568
http://dx.doi.org/10.3389/fgene.2022.867856
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