{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:04:34Z","timestamp":1770681874701,"version":"3.49.0"},"reference-count":64,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Next-generation sequencing (NGS) technologies have been proposed as a first-line test for the diagnosis of inborn errors of metabolism (IEM), a group of genetically heterogeneous disorders with overlapping or nonspecific phenotypes. Over a 3-year period, we prospectively analyzed 311 pediatric patients with a suspected IEM using four targeted gene panels. The rate of positive diagnosis was 61.86% for intermediary metabolism defects, 32.84% for complex molecular defects, 19% for hypoglycemic\/hyperglycemic events, and 17% for mitochondrial diseases, and a conclusive molecular diagnosis was established in 2\u20134 weeks. Forty-one patients for whom negative results were obtained with the mitochondrial diseases panel underwent subsequent analyses using the NeuroSeq panel, which groups all genes from the individual panels together with genes associated with neurological disorders (1870 genes in total). This achieved a diagnostic rate of 32%. We next evaluated the utility of a tool, Phenomizer, for differential diagnosis, and established a correlation between phenotype and molecular findings in 39.3% of patients. Finally, we evaluated the mutational architecture of the genes analyzed by determining z-scores, loss-of-function observed\/expected upper bound fraction (LOEUF), and haploinsufficiency (HI) scores. In summary, targeted gene panels for specific groups of IEMs enabled rapid and effective diagnosis, which is critical for the therapeutic management of IEM patients.<\/jats:p>","DOI":"10.3390\/genes12081262","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T04:13:54Z","timestamp":1629346434000},"page":"1262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Utility of Gene Panels for the Diagnosis of Inborn Errors of Metabolism in a Metabolic Reference Center"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1431-4644","authenticated-orcid":false,"given":"Sofia","family":"Barbosa-Gouveia","sequence":"first","affiliation":[{"name":"Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Paediatrics, IDIS-Health Research Institute of Santiago de Compostela, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), European Reference Network for Hereditary Metabolic Disorders (MetabERN), Santiago de Compostela University Clinical Hospital, 15704 Santiago de Compostela, Spain"}]},{"given":"Mar\u00eda E.","family":"V\u00e1zquez-Mosquera","sequence":"additional","affiliation":[{"name":"Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Paediatrics, IDIS-Health Research Institute of Santiago de Compostela, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), European Reference Network for Hereditary Metabolic Disorders (MetabERN), Santiago de Compostela University Clinical Hospital, 15704 Santiago de Compostela, Spain"}]},{"given":"Emiliano","family":"Gonz\u00e1lez-Vioque","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Puerta de Hierro-Majadahonda University Hospital, 28222 Majadahonda, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3735-1341","authenticated-orcid":false,"given":"Jos\u00e9 V.","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Paediatrics, IDIS-Health Research Institute of Santiago de Compostela, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), European Reference Network for Hereditary Metabolic Disorders (MetabERN), Santiago de Compostela University Clinical Hospital, 15704 Santiago de Compostela, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0699-9073","authenticated-orcid":false,"given":"Roi","family":"Chans","sequence":"additional","affiliation":[{"name":"Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Paediatrics, IDIS-Health Research Institute of Santiago de Compostela, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), European Reference Network for Hereditary Metabolic Disorders (MetabERN), Santiago de Compostela University Clinical Hospital, 15704 Santiago de Compostela, Spain"}]},{"given":"Francisco","family":"Laranjeira","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Unit, Centro de Gen\u00e9tica M\u00e9dica Doutor Jacinto Magalh\u00e3es, 4050-466 Porto, Portugal"}]},{"given":"Esmeralda","family":"Martins","sequence":"additional","affiliation":[{"name":"Centro Materno-Infantil do Norte, Centro Hospitalar Universit\u00e1rio do Porto (CHUP), Coordinator of the Centro de Refer\u00eancia de Doen\u00e7as Heredit\u00e1rias do Metabolismo do CHUP, 4050-466 Porto, Portugal"}]},{"given":"Ana Cristina","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Hospital D. Estef\u00e2nia, Centro Hospitalar de Lisboa Central (CHLC), Coordinator of the Centro de Refer\u00eancia de Doen\u00e7as Heredit\u00e1rias do Metabolismo do CHLC, 1169-050 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5541-6968","authenticated-orcid":false,"given":"Alejandro","family":"Avila-Alvarez","sequence":"additional","affiliation":[{"name":"Neonatology Unit, Pediatrics Department, Complexo Hospitalario Universitario de A Coru\u00f1a, SERGAS, 15006 A Coru\u00f1a, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4861-9905","authenticated-orcid":false,"given":"Mar\u00eda L.","family":"Couce","sequence":"additional","affiliation":[{"name":"Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Paediatrics, IDIS-Health Research Institute of Santiago de Compostela, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), European Reference Network for Hereditary Metabolic Disorders (MetabERN), Santiago de Compostela University Clinical Hospital, 15704 Santiago de Compostela, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tebani, A., Abily-Donval, L., Afonso, C., Marret, S., and Bekri, S. 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