Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience
Introduction: Mitochondrial fatty acid oxidation disorders (FAODs) are a heterogeneous group of hereditary autosomal recessive diseases included in newborn screening (NBS) program in Italy. The aim of this study was to analyse FAODs cases, identified either clinically or by NBS,for clinical and gene...
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Elsevier
2020-09-01
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Series: | Molecular Genetics and Metabolism Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426920300781 |
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language |
English |
format |
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DOAJ |
author |
A. Maguolo G. Rodella A. Dianin R. Nurti I. Monge E. Rigotti G. Cantalupo L. Salviati S. Tucci F. Pellegrini G. Molinaro F. Lupi P. Tonin A. Pasini N. Campostrini F. Ion Popa F. Teofoli M. Vincenzi M. Camilot G. Piacentini A. Bordugo |
spellingShingle |
A. Maguolo G. Rodella A. Dianin R. Nurti I. Monge E. Rigotti G. Cantalupo L. Salviati S. Tucci F. Pellegrini G. Molinaro F. Lupi P. Tonin A. Pasini N. Campostrini F. Ion Popa F. Teofoli M. Vincenzi M. Camilot G. Piacentini A. Bordugo Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience Molecular Genetics and Metabolism Reports Fatty acid oxidation defects Expanded newborn screening Enzymatic activity Synergistic heterozygosity Hypoglycaemia Myopathy |
author_facet |
A. Maguolo G. Rodella A. Dianin R. Nurti I. Monge E. Rigotti G. Cantalupo L. Salviati S. Tucci F. Pellegrini G. Molinaro F. Lupi P. Tonin A. Pasini N. Campostrini F. Ion Popa F. Teofoli M. Vincenzi M. Camilot G. Piacentini A. Bordugo |
author_sort |
A. Maguolo |
title |
Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience |
title_short |
Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience |
title_full |
Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience |
title_fullStr |
Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience |
title_full_unstemmed |
Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience |
title_sort |
diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: a single centre experience |
publisher |
Elsevier |
series |
Molecular Genetics and Metabolism Reports |
issn |
2214-4269 |
publishDate |
2020-09-01 |
description |
Introduction: Mitochondrial fatty acid oxidation disorders (FAODs) are a heterogeneous group of hereditary autosomal recessive diseases included in newborn screening (NBS) program in Italy. The aim of this study was to analyse FAODs cases, identified either clinically or by NBS,for clinical and genetic characterization and to evaluate a five years' experience of NBS, in the attempt to figure out the complexity of genotype-phenotype correlation and to confirm the clinical impact of NBS in our centre experience. Materials and methods: We analysed FAODs patients diagnosed either by NBS or clinically, followed since February 2014 to April 2019 at the Regional Screening Centre and Inherited Metabolic Diseases Unit of Verona. Diagnosis was confirmed by plasma acylcarnitines, urinary organic acids, enzymatic and genetic testing. For not clear genotypes due to the presence of variants of uncertain significance, in silico predictive tools have been used as well as enzymatic activity assays. Patients underwent clinical, nutritional and biochemical follow up. Results: We diagnosed 30 patients with FAODs. 20 by NBS: 3 CUD, 6 SCADD, 5 MCADD, 4 VLCADD, 2 MADD. Overall incidence of FAODs diagnosed by NBS was 1:4316 newborns. No one reported complications during the follow up period. 10 patients were diagnosed clinically: 2 CUD, 2 CPT2D, 1 VLCADD, 5 MADD. Mean age at diagnosis was 29.3 years. Within this group, complications or symptoms were reported at diagnosis, but not during follow-up. 12 mutations not previously reported in literature were found, all predicted as pathogenic or likely pathogenic. Discussion and conclusions: Our study highlighted the great phenotypic variability and molecular heterogeneity of FAODs and confirmed the importance of a tailored follow up and treatment. Despite the short duration of follow up, early identification by NBS prevented diseases related complications and resulted in normal growth and psycho-motor development as well. |
topic |
Fatty acid oxidation defects Expanded newborn screening Enzymatic activity Synergistic heterozygosity Hypoglycaemia Myopathy |
url |
http://www.sciencedirect.com/science/article/pii/S2214426920300781 |
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doaj-d2a3f4cedf0c4c79a6ef4ce17452171d2020-11-25T03:52:44ZengElsevierMolecular Genetics and Metabolism Reports2214-42692020-09-0124100632Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experienceA. Maguolo0G. Rodella1A. Dianin2R. Nurti3I. Monge4E. Rigotti5G. Cantalupo6L. Salviati7S. Tucci8F. Pellegrini9G. Molinaro10F. Lupi11P. Tonin12A. Pasini13N. Campostrini14F. Ion Popa15F. Teofoli16M. Vincenzi17M. Camilot18G. Piacentini19A. Bordugo20Department of Mother and Child, Pediatric Clinic, University Hospital of Verona, Verona, ItalyDepartment of Mother and Child, Pediatric Clinic, University Hospital of Verona, Verona, Italy; Inherited Metabolic Diseases Unit and Regional Centre for Newborn Screening, Diagnosis and Treatment of Inherited Metabolic Diseases and Congenital Endocrine Diseases, Azienda Ospedaliera Universitaria Integrata, Verona, ItalyDepartment of Mother and Child, Pediatric Clinic, University Hospital of Verona, Verona, Italy; Inherited Metabolic Diseases Unit and Regional Centre for Newborn Screening, Diagnosis and Treatment of Inherited Metabolic Diseases and Congenital Endocrine Diseases, Azienda Ospedaliera Universitaria Integrata, Verona, ItalyDepartment of Mother and Child, Pediatric Clinic, University Hospital of Verona, Verona, Italy; Inherited Metabolic Diseases Unit and Regional Centre for Newborn Screening, Diagnosis and Treatment of Inherited Metabolic Diseases and Congenital Endocrine Diseases, Azienda Ospedaliera Universitaria Integrata, Verona, ItalyDepartment of Mother and Child, Pediatric Clinic, University Hospital of Verona, Verona, Italy; Inherited Metabolic Diseases Unit and Regional Centre for Newborn Screening, Diagnosis and Treatment of Inherited Metabolic Diseases and Congenital Endocrine Diseases, Azienda Ospedaliera Universitaria Integrata, Verona, ItalyDepartment of Mother and Child, Pediatric Clinic, University Hospital of Verona, Verona, ItalyDepartment of Surgical Sciences, Dentistry, Gynaecology and Paediatrics, Division of Child Neuropsychiatry, University of Verona, Verona, ItalyClinical Genetics Unit, Department of Women and Children's Health, University of Padova, Padua, Italy; IRP Città della Speranza, Padua, ItalyLaboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics and Adolescent Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, GermanyNeonatal Intensive Care unit, Azienda Sanitaria Alto Adige, Bolzano, ItalyNeonatal Intensive Care unit, Azienda Sanitaria Alto Adige, Bolzano, ItalyNeonatal Intensive Care unit, Azienda Sanitaria Alto Adige, Bolzano, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, Section of Clinical Neurology, University of Verona, Verona, ItalyDepartment of Pediatrics, Regional Centre for Newborn Screening, Diagnosis and Treatment of Inherited Metabolic Diseases and Congenital Endocrine Diseases, AOUI, Verona, ItalyDepartment of Pediatrics, Regional Centre for Newborn Screening, Diagnosis and Treatment of Inherited Metabolic Diseases and Congenital Endocrine Diseases, AOUI, Verona, ItalyDepartment of Pediatrics, Regional Centre for Newborn Screening, Diagnosis and Treatment of Inherited Metabolic Diseases and Congenital Endocrine Diseases, AOUI, Verona, ItalyDepartment of Pediatrics, Regional Centre for Newborn Screening, Diagnosis and Treatment of Inherited Metabolic Diseases and Congenital Endocrine Diseases, AOUI, Verona, ItalyDepartment of Pediatrics, Regional Centre for Newborn Screening, Diagnosis and Treatment of Inherited Metabolic Diseases and Congenital Endocrine Diseases, AOUI, Verona, ItalyDepartment of Pediatrics, Regional Centre for Newborn Screening, Diagnosis and Treatment of Inherited Metabolic Diseases and Congenital Endocrine Diseases, AOUI, Verona, ItalyDepartment of Mother and Child, Pediatric Clinic, University Hospital of Verona, Verona, ItalyDepartment of Mother and Child, Pediatric Clinic, University Hospital of Verona, Verona, Italy; Inherited Metabolic Diseases Unit and Regional Centre for Newborn Screening, Diagnosis and Treatment of Inherited Metabolic Diseases and Congenital Endocrine Diseases, Azienda Ospedaliera Universitaria Integrata, Verona, Italy; Corresponding author at: Verona 1 37126, Italy.Introduction: Mitochondrial fatty acid oxidation disorders (FAODs) are a heterogeneous group of hereditary autosomal recessive diseases included in newborn screening (NBS) program in Italy. The aim of this study was to analyse FAODs cases, identified either clinically or by NBS,for clinical and genetic characterization and to evaluate a five years' experience of NBS, in the attempt to figure out the complexity of genotype-phenotype correlation and to confirm the clinical impact of NBS in our centre experience. Materials and methods: We analysed FAODs patients diagnosed either by NBS or clinically, followed since February 2014 to April 2019 at the Regional Screening Centre and Inherited Metabolic Diseases Unit of Verona. Diagnosis was confirmed by plasma acylcarnitines, urinary organic acids, enzymatic and genetic testing. For not clear genotypes due to the presence of variants of uncertain significance, in silico predictive tools have been used as well as enzymatic activity assays. Patients underwent clinical, nutritional and biochemical follow up. Results: We diagnosed 30 patients with FAODs. 20 by NBS: 3 CUD, 6 SCADD, 5 MCADD, 4 VLCADD, 2 MADD. Overall incidence of FAODs diagnosed by NBS was 1:4316 newborns. No one reported complications during the follow up period. 10 patients were diagnosed clinically: 2 CUD, 2 CPT2D, 1 VLCADD, 5 MADD. Mean age at diagnosis was 29.3 years. Within this group, complications or symptoms were reported at diagnosis, but not during follow-up. 12 mutations not previously reported in literature were found, all predicted as pathogenic or likely pathogenic. Discussion and conclusions: Our study highlighted the great phenotypic variability and molecular heterogeneity of FAODs and confirmed the importance of a tailored follow up and treatment. Despite the short duration of follow up, early identification by NBS prevented diseases related complications and resulted in normal growth and psycho-motor development as well.http://www.sciencedirect.com/science/article/pii/S2214426920300781Fatty acid oxidation defectsExpanded newborn screeningEnzymatic activitySynergistic heterozygosityHypoglycaemiaMyopathy |