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Biochemical diagnosis of aromatic-L-amino acid decarboxylase deficiency (AADCD) by assay of AADC activity in plasma using liquid chromatography/tandem mass spectrometry
Aromatic l-amino acid decarboxylase (AADC, EC 4.1.1.28) deficiency is a rare genetic disorder characterized by developmental delay, oculogyric crises, autonomic dysfunction and other problems, caused by biallelic mutations in the DDC gene leading to deficient activity of aromatic l-amino acid decarb...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234702/ https://www.ncbi.nlm.nih.gov/pubmed/35769135 http://dx.doi.org/10.1016/j.ymgmr.2022.100888 |
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author | Civallero, Gabriel Kubaski, Francyne Pereira, Danilo Rübensam, Gabriel Herbst, Zackary M. Silva, Camilo Trapp, Franciele B. Poletto, Edina Faqueti, Larissa Iop, Gabrielle Soares, Juliano van der Linden, Vanessa van der Linden, Helio Lourenço, Charles M. Giugliani, Roberto |
author_facet | Civallero, Gabriel Kubaski, Francyne Pereira, Danilo Rübensam, Gabriel Herbst, Zackary M. Silva, Camilo Trapp, Franciele B. Poletto, Edina Faqueti, Larissa Iop, Gabrielle Soares, Juliano van der Linden, Vanessa van der Linden, Helio Lourenço, Charles M. Giugliani, Roberto |
author_sort | Civallero, Gabriel |
collection | PubMed |
description | Aromatic l-amino acid decarboxylase (AADC, EC 4.1.1.28) deficiency is a rare genetic disorder characterized by developmental delay, oculogyric crises, autonomic dysfunction and other problems, caused by biallelic mutations in the DDC gene leading to deficient activity of aromatic l-amino acid decarboxylase, an enzyme involved in the formation of important neurotransmitters, such as dopamine and serotonin. A clinical development program of gene therapy for AADC deficiency is ongoing. An important step for the success of this therapy is the early and precise identification of the affected individuals, but it has been estimated that around 90% of the cases remain undiagnosed. The availability measurement of the AADC activity is mandatory for an accurate biochemical diagnosis. Based on these statements, our objectives were to develop a liquid chromatography tandem mass spectrometry (LC-MS/MS) method suitable for the determination of the AADC activity, and to evaluate its capacity to confirm the deficiency of AADC in potential patients in Brazil. The AADC activities were measured in plasma samples of seven AADC deficient patients and 35 healthy controls, after enzymatic reaction and LC-MS/MS analysis of dopamine, the main reaction product. The results obtained showed clear discrimination between confirmed AADC deficient patients and healthy controls. The method presented here could be incorporated in the IEM laboratories for confirmation of the diagnosis of when a suspicion of AADC deficiency is present due to clinical signs and/or abnormal biomarkers, including when an increased level of 3-O-methyldopa (3-OMD) is found in dried blood spots (DBS) samples from high-risk patients or from newborn screening programs. |
format | Online Article Text |
id | pubmed-9234702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-92347022022-06-28 Biochemical diagnosis of aromatic-L-amino acid decarboxylase deficiency (AADCD) by assay of AADC activity in plasma using liquid chromatography/tandem mass spectrometry Civallero, Gabriel Kubaski, Francyne Pereira, Danilo Rübensam, Gabriel Herbst, Zackary M. Silva, Camilo Trapp, Franciele B. Poletto, Edina Faqueti, Larissa Iop, Gabrielle Soares, Juliano van der Linden, Vanessa van der Linden, Helio Lourenço, Charles M. Giugliani, Roberto Mol Genet Metab Rep Research Paper Aromatic l-amino acid decarboxylase (AADC, EC 4.1.1.28) deficiency is a rare genetic disorder characterized by developmental delay, oculogyric crises, autonomic dysfunction and other problems, caused by biallelic mutations in the DDC gene leading to deficient activity of aromatic l-amino acid decarboxylase, an enzyme involved in the formation of important neurotransmitters, such as dopamine and serotonin. A clinical development program of gene therapy for AADC deficiency is ongoing. An important step for the success of this therapy is the early and precise identification of the affected individuals, but it has been estimated that around 90% of the cases remain undiagnosed. The availability measurement of the AADC activity is mandatory for an accurate biochemical diagnosis. Based on these statements, our objectives were to develop a liquid chromatography tandem mass spectrometry (LC-MS/MS) method suitable for the determination of the AADC activity, and to evaluate its capacity to confirm the deficiency of AADC in potential patients in Brazil. The AADC activities were measured in plasma samples of seven AADC deficient patients and 35 healthy controls, after enzymatic reaction and LC-MS/MS analysis of dopamine, the main reaction product. The results obtained showed clear discrimination between confirmed AADC deficient patients and healthy controls. The method presented here could be incorporated in the IEM laboratories for confirmation of the diagnosis of when a suspicion of AADC deficiency is present due to clinical signs and/or abnormal biomarkers, including when an increased level of 3-O-methyldopa (3-OMD) is found in dried blood spots (DBS) samples from high-risk patients or from newborn screening programs. Elsevier 2022-06-21 /pmc/articles/PMC9234702/ /pubmed/35769135 http://dx.doi.org/10.1016/j.ymgmr.2022.100888 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Civallero, Gabriel Kubaski, Francyne Pereira, Danilo Rübensam, Gabriel Herbst, Zackary M. Silva, Camilo Trapp, Franciele B. Poletto, Edina Faqueti, Larissa Iop, Gabrielle Soares, Juliano van der Linden, Vanessa van der Linden, Helio Lourenço, Charles M. Giugliani, Roberto Biochemical diagnosis of aromatic-L-amino acid decarboxylase deficiency (AADCD) by assay of AADC activity in plasma using liquid chromatography/tandem mass spectrometry |
title | Biochemical diagnosis of aromatic-L-amino acid decarboxylase deficiency (AADCD) by assay of AADC activity in plasma using liquid chromatography/tandem mass spectrometry |
title_full | Biochemical diagnosis of aromatic-L-amino acid decarboxylase deficiency (AADCD) by assay of AADC activity in plasma using liquid chromatography/tandem mass spectrometry |
title_fullStr | Biochemical diagnosis of aromatic-L-amino acid decarboxylase deficiency (AADCD) by assay of AADC activity in plasma using liquid chromatography/tandem mass spectrometry |
title_full_unstemmed | Biochemical diagnosis of aromatic-L-amino acid decarboxylase deficiency (AADCD) by assay of AADC activity in plasma using liquid chromatography/tandem mass spectrometry |
title_short | Biochemical diagnosis of aromatic-L-amino acid decarboxylase deficiency (AADCD) by assay of AADC activity in plasma using liquid chromatography/tandem mass spectrometry |
title_sort | biochemical diagnosis of aromatic-l-amino acid decarboxylase deficiency (aadcd) by assay of aadc activity in plasma using liquid chromatography/tandem mass spectrometry |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234702/ https://www.ncbi.nlm.nih.gov/pubmed/35769135 http://dx.doi.org/10.1016/j.ymgmr.2022.100888 |
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