Lymphocyte Medium-Chain Acyl-CoA Dehydrogenase Activity and Its Potential as a Diagnostic Confirmation Tool in Newborn Screening Cases
The determination of acylcarnitines (AC) in dried blood spots (DBS) by tandem mass spectrometry in newborn screening (NBS) programs has enabled medium-chain acyl-coA dehydrogenase deficiency (MCADD) to be identified in presymptomatic newborns. Nevertheless, different confirmatory tests must be perfo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/10/2933 |
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| author | Patricia Alcaide Isaac Ferrer-López Leticia Gutierrez Fatima Leal Elena Martín-Hernández Pilar Quijada-Fraile Marcello Bellusci Ana Moráis Consuelo Pedrón-Giner Dolores Rausell Patricia Correcher María Unceta Sinziana Stanescu Magdalena Ugarte Pedro Ruiz-Sala Belén Pérez |
| author_facet | Patricia Alcaide Isaac Ferrer-López Leticia Gutierrez Fatima Leal Elena Martín-Hernández Pilar Quijada-Fraile Marcello Bellusci Ana Moráis Consuelo Pedrón-Giner Dolores Rausell Patricia Correcher María Unceta Sinziana Stanescu Magdalena Ugarte Pedro Ruiz-Sala Belén Pérez |
| author_sort | Patricia Alcaide |
| collection | DOAJ |
| description | The determination of acylcarnitines (AC) in dried blood spots (DBS) by tandem mass spectrometry in newborn screening (NBS) programs has enabled medium-chain acyl-coA dehydrogenase deficiency (MCADD) to be identified in presymptomatic newborns. Nevertheless, different confirmatory tests must be performed to confirm the diagnosis. In this work, we have collected and analyzed the NBS results and confirmatory test results (plasma AC, molecular findings, and lymphocyte MCAD activity) of forty individuals, correlating them with clinical outcomes and treatment, with the aim of obtaining useful diagnostic information that could be applied in the follow-up of the patients. Our results led us to classify patients into two groups. The first group (14 cases) had high increased octanoylcarnitine (C8) levels, biallelic pathogenic variants, and severe impaired enzyme activity (<10% of the intra-assay control (IAC)); all of these cases received nutritional therapy and required carnitine supplementation during follow-up, representing the most severe form of the disease. The second group (16 patients) was a heterogeneous group presenting moderate increases in C8, biallelic likely pathogenic/pathogenic variants, and intermediate activity (<41% IAC). All of them are currently asymptomatic and could be considered as having a milder form of the disease. Finally, eight cases presented a normal–mild increase in plasma C8, with only one pathogenic variant detected, and high–intermediate residual activity (15–100%). Based on our results, we confirm that combined evaluation of acylcarnitine profiles, genetic findings, and residual enzyme activities proves useful in predicting the risk of future metabolic decompensation, in making decisions regarding future treatment or follow-up, and also in confirming the clinical effects of unknown clinical variants. |
| first_indexed | 2024-03-10T03:39:24Z |
| format | Article |
| id | doaj.art-37583be35aaa4e7ba9b10ed26dc09729 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T03:39:24Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-37583be35aaa4e7ba9b10ed26dc097292023-11-23T11:37:06ZengMDPI AGJournal of Clinical Medicine2077-03832022-05-011110293310.3390/jcm11102933Lymphocyte Medium-Chain Acyl-CoA Dehydrogenase Activity and Its Potential as a Diagnostic Confirmation Tool in Newborn Screening CasesPatricia Alcaide0Isaac Ferrer-López1Leticia Gutierrez2Fatima Leal3Elena Martín-Hernández4Pilar Quijada-Fraile5Marcello Bellusci6Ana Moráis7Consuelo Pedrón-Giner8Dolores Rausell9Patricia Correcher10María Unceta11Sinziana Stanescu12Magdalena Ugarte13Pedro Ruiz-Sala14Belén Pérez15Centro de Diagnóstico de Enfermedades Moleculares (CEDEM), Universidad Autónoma Madrid, CIBERER, IDIPAZ, 28049 Madrid, SpainCentro de Diagnóstico de Enfermedades Moleculares (CEDEM), Universidad Autónoma Madrid, CIBERER, IDIPAZ, 28049 Madrid, SpainCentro de Diagnóstico de Enfermedades Moleculares (CEDEM), Universidad Autónoma Madrid, CIBERER, IDIPAZ, 28049 Madrid, SpainCentro de Diagnóstico de Enfermedades Moleculares (CEDEM), Universidad Autónoma Madrid, CIBERER, IDIPAZ, 28049 Madrid, SpainCentro de Referencia Nacional (CSUR) y Europeo (MetabERN) para Enfermedades Metabólicas, Hospital Universitario 12 de Octubre, 28041 Madrid, SpainCentro de Referencia Nacional (CSUR) y Europeo (MetabERN) para Enfermedades Metabólicas, Hospital Universitario 12 de Octubre, 28041 Madrid, SpainCentro de Referencia Nacional (CSUR) y Europeo (MetabERN) para Enfermedades Metabólicas, Hospital Universitario 12 de Octubre, 28041 Madrid, SpainUnidad de Nutrición Infantil y Enfermedades Metabólicas, Hospital Universitario Infantil La Paz, 28046 Madrid, SpainSección de Gastroenterología y Nutrición, Hospital Infantil Universitario Niño Jesús, 28009 Madrid, SpainLaboratorio de Metabolopatías, Servicio de Análisis Clínicos, Hospital Universitario La Fe, 46026 Valencia, SpainLaboratorio de Metabolopatías, Servicio de Análisis Clínicos, Hospital Universitario La Fe, 46026 Valencia, SpainAnálisis Clínicos, Servicio de Bioquímica, Unidad de Enfermedades Metabólicas, Hospital Universitario de Cruces, 48903 Barakaldo, SpainServicio de Pediatría, Unidad de Enfermedades Metabólicas, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, SpainCentro de Diagnóstico de Enfermedades Moleculares (CEDEM), Universidad Autónoma Madrid, CIBERER, IDIPAZ, 28049 Madrid, SpainCentro de Diagnóstico de Enfermedades Moleculares (CEDEM), Universidad Autónoma Madrid, CIBERER, IDIPAZ, 28049 Madrid, SpainCentro de Diagnóstico de Enfermedades Moleculares (CEDEM), Universidad Autónoma Madrid, CIBERER, IDIPAZ, 28049 Madrid, SpainThe determination of acylcarnitines (AC) in dried blood spots (DBS) by tandem mass spectrometry in newborn screening (NBS) programs has enabled medium-chain acyl-coA dehydrogenase deficiency (MCADD) to be identified in presymptomatic newborns. Nevertheless, different confirmatory tests must be performed to confirm the diagnosis. In this work, we have collected and analyzed the NBS results and confirmatory test results (plasma AC, molecular findings, and lymphocyte MCAD activity) of forty individuals, correlating them with clinical outcomes and treatment, with the aim of obtaining useful diagnostic information that could be applied in the follow-up of the patients. Our results led us to classify patients into two groups. The first group (14 cases) had high increased octanoylcarnitine (C8) levels, biallelic pathogenic variants, and severe impaired enzyme activity (<10% of the intra-assay control (IAC)); all of these cases received nutritional therapy and required carnitine supplementation during follow-up, representing the most severe form of the disease. The second group (16 patients) was a heterogeneous group presenting moderate increases in C8, biallelic likely pathogenic/pathogenic variants, and intermediate activity (<41% IAC). All of them are currently asymptomatic and could be considered as having a milder form of the disease. Finally, eight cases presented a normal–mild increase in plasma C8, with only one pathogenic variant detected, and high–intermediate residual activity (15–100%). Based on our results, we confirm that combined evaluation of acylcarnitine profiles, genetic findings, and residual enzyme activities proves useful in predicting the risk of future metabolic decompensation, in making decisions regarding future treatment or follow-up, and also in confirming the clinical effects of unknown clinical variants.https://www.mdpi.com/2077-0383/11/10/2933acylcarnitineslymphocyte enzyme activitymedium-chain acyl-CoA dehydrogenasenewborn screeningfatty acid oxidation |
| spellingShingle | Patricia Alcaide Isaac Ferrer-López Leticia Gutierrez Fatima Leal Elena Martín-Hernández Pilar Quijada-Fraile Marcello Bellusci Ana Moráis Consuelo Pedrón-Giner Dolores Rausell Patricia Correcher María Unceta Sinziana Stanescu Magdalena Ugarte Pedro Ruiz-Sala Belén Pérez Lymphocyte Medium-Chain Acyl-CoA Dehydrogenase Activity and Its Potential as a Diagnostic Confirmation Tool in Newborn Screening Cases Journal of Clinical Medicine acylcarnitines lymphocyte enzyme activity medium-chain acyl-CoA dehydrogenase newborn screening fatty acid oxidation |
| title | Lymphocyte Medium-Chain Acyl-CoA Dehydrogenase Activity and Its Potential as a Diagnostic Confirmation Tool in Newborn Screening Cases |
| title_full | Lymphocyte Medium-Chain Acyl-CoA Dehydrogenase Activity and Its Potential as a Diagnostic Confirmation Tool in Newborn Screening Cases |
| title_fullStr | Lymphocyte Medium-Chain Acyl-CoA Dehydrogenase Activity and Its Potential as a Diagnostic Confirmation Tool in Newborn Screening Cases |
| title_full_unstemmed | Lymphocyte Medium-Chain Acyl-CoA Dehydrogenase Activity and Its Potential as a Diagnostic Confirmation Tool in Newborn Screening Cases |
| title_short | Lymphocyte Medium-Chain Acyl-CoA Dehydrogenase Activity and Its Potential as a Diagnostic Confirmation Tool in Newborn Screening Cases |
| title_sort | lymphocyte medium chain acyl coa dehydrogenase activity and its potential as a diagnostic confirmation tool in newborn screening cases |
| topic | acylcarnitines lymphocyte enzyme activity medium-chain acyl-CoA dehydrogenase newborn screening fatty acid oxidation |
| url | https://www.mdpi.com/2077-0383/11/10/2933 |
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