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Normal reference ranges for urinary δ‐aminolevulinic acid and porphobilinogen levels
Acute hepatic porphyria (AHP) is a family of rare, serious, and potentially life‐threatening metabolic disorders caused by mutations in genes encoding enzymes involved in hepatic heme biosynthesis. AHP is characterized by accumulation of neurotoxic heme intermediates, δ‐aminolevulinic acid (ALA), an...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802627/ https://www.ncbi.nlm.nih.gov/pubmed/33473344 http://dx.doi.org/10.1002/jmd2.12173 |
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author | Agarwal, Sagar Habtemarium, Bahru Xu, Yuanxin Simon, Amy R. Kim, Jae B. Robbie, Gabriel J. |
author_facet | Agarwal, Sagar Habtemarium, Bahru Xu, Yuanxin Simon, Amy R. Kim, Jae B. Robbie, Gabriel J. |
author_sort | Agarwal, Sagar |
collection | PubMed |
description | Acute hepatic porphyria (AHP) is a family of rare, serious, and potentially life‐threatening metabolic disorders caused by mutations in genes encoding enzymes involved in hepatic heme biosynthesis. AHP is characterized by accumulation of neurotoxic heme intermediates, δ‐aminolevulinic acid (ALA), and porphobilinogen (PBG), which are thought to be causal for the disease manifestations. Novel therapeutic treatments such as givosiran, an RNA interference therapeutic that was recently approved for treatment of adults with AHP, are focused on reducing the levels of ALA and PBG in patients toward levels observed in a healthy population. While there are two published reports on the distribution of urinary ALA and PBG levels in healthy subjects, these lacked the required details to enable the calculation of reference limits for ALA and PBG. Therefore, urinary ALA and PBG levels were quantified in 150 healthy subjects using a validated liquid chromatography tandem mass spectrometry (LC‐MS/MS) method that is highly sensitive, specific, accurate, and reproducible. These data were used to establish the upper limit of normal (ULN) values for ALA and PBG as 1.47 and 0.137 mmol/mol Cr, respectively. Relative to these ULN values, baseline urinary ALA and PBG levels in AHP patients were found to be 9.3‐ to 12‐fold, and 238‐ to 336‐fold higher, respectively. Results from this study can serve as a guide to assess the effectiveness of therapeutic interventions in lowering ALA and PBG. |
format | Online Article Text |
id | pubmed-7802627 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78026272021-01-19 Normal reference ranges for urinary δ‐aminolevulinic acid and porphobilinogen levels Agarwal, Sagar Habtemarium, Bahru Xu, Yuanxin Simon, Amy R. Kim, Jae B. Robbie, Gabriel J. JIMD Rep Research Reports Acute hepatic porphyria (AHP) is a family of rare, serious, and potentially life‐threatening metabolic disorders caused by mutations in genes encoding enzymes involved in hepatic heme biosynthesis. AHP is characterized by accumulation of neurotoxic heme intermediates, δ‐aminolevulinic acid (ALA), and porphobilinogen (PBG), which are thought to be causal for the disease manifestations. Novel therapeutic treatments such as givosiran, an RNA interference therapeutic that was recently approved for treatment of adults with AHP, are focused on reducing the levels of ALA and PBG in patients toward levels observed in a healthy population. While there are two published reports on the distribution of urinary ALA and PBG levels in healthy subjects, these lacked the required details to enable the calculation of reference limits for ALA and PBG. Therefore, urinary ALA and PBG levels were quantified in 150 healthy subjects using a validated liquid chromatography tandem mass spectrometry (LC‐MS/MS) method that is highly sensitive, specific, accurate, and reproducible. These data were used to establish the upper limit of normal (ULN) values for ALA and PBG as 1.47 and 0.137 mmol/mol Cr, respectively. Relative to these ULN values, baseline urinary ALA and PBG levels in AHP patients were found to be 9.3‐ to 12‐fold, and 238‐ to 336‐fold higher, respectively. Results from this study can serve as a guide to assess the effectiveness of therapeutic interventions in lowering ALA and PBG. John Wiley & Sons, Inc. 2020-10-01 /pmc/articles/PMC7802627/ /pubmed/33473344 http://dx.doi.org/10.1002/jmd2.12173 Text en © 2020 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Reports Agarwal, Sagar Habtemarium, Bahru Xu, Yuanxin Simon, Amy R. Kim, Jae B. Robbie, Gabriel J. Normal reference ranges for urinary δ‐aminolevulinic acid and porphobilinogen levels |
title | Normal reference ranges for urinary δ‐aminolevulinic acid and porphobilinogen levels |
title_full | Normal reference ranges for urinary δ‐aminolevulinic acid and porphobilinogen levels |
title_fullStr | Normal reference ranges for urinary δ‐aminolevulinic acid and porphobilinogen levels |
title_full_unstemmed | Normal reference ranges for urinary δ‐aminolevulinic acid and porphobilinogen levels |
title_short | Normal reference ranges for urinary δ‐aminolevulinic acid and porphobilinogen levels |
title_sort | normal reference ranges for urinary δ‐aminolevulinic acid and porphobilinogen levels |
topic | Research Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802627/ https://www.ncbi.nlm.nih.gov/pubmed/33473344 http://dx.doi.org/10.1002/jmd2.12173 |
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