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
| Autor: | Marta Camilot, R. Nurti, Gaetano Cantalupo, Alice Maguolo, F. Lupi, Erika Rigotti, Giorgio Piacentini, Francesca Teofoli, Andrea Pasini, F. Ion Popa, Monica Vincenzi, Paola Tonin, Giulia Rodella, Grazia Molinaro, Leonardo Salviati, A. Dianin, F. Pellegrini, Natascia Campostrini, A. Bordugo, I. Monge, Sara Tucci |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
FAODs
fatty acid oxidation disorders Pediatrics MCADD medium-chain acyl-CoA dehydrogenase deficiency MADD multiple acyl-CoA dehydrogenase deficiency ALT TFPD trifunctional protein deficiency polymerase chain reaction Myopathy DBS medium-chain acyl-CoA dehydrogenase deficiency CUD Mitochondrial fatty acid CACTD Expanded newborn screening NBS newborn screening DNA Deoxyribonucleic acid 0302 clinical medicine Endocrinology NBS PCR polymerase chain reaction carnitine uptake defect Genotype very-long-chain acyl-CoA dehydrogenase deficiency SCADD Medicine FAODs lcsh:QH301-705.5 LCHADD next generation sequencing trifunctional protein deficiency SCADD short chain acyl-CoA dehydrogenase deficiency 0303 health sciences DBS dried blood spots Synergistic heterozygosity lcsh:R5-920 medicine.diagnostic_test Deoxyribonucleic acid LCHADD Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency Incidence (epidemiology) 030305 genetics & heredity PCR CK NGS dried blood spots medicine.symptom VLCADD AST Aspartate aminotransferase lcsh:Medicine (General) Research Paper medicine.medical_specialty fatty acid oxidation disorders Urinary system Enzymatic activity Fatty acid oxidation defects Hypoglycaemia Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency MCADD Aspartate aminotransferase carnitine palmitoyl-CoA transferase 1/2 deficiency short chain acyl-CoA dehydrogenase deficiency 03 medical and health sciences multiple acyl-CoA dehydrogenase deficiency CACTD carnitine-acylcarnitine translocase deficiency TFPD tandem mass spectrometry Genetics CUD carnitine uptake defect CPT1/2 D carnitine palmitoyl-CoA transferase 1/2 deficiency Molecular Biology AST Genetic testing Newborn screening business.industry creatine kinase newborn screening ALT Alanine aminotransferase CPT1/2 D MADD NGS next generation sequencing carnitine-acylcarnitine translocase deficiency DNA medicine.disease lcsh:Biology (General) VLCADD very-long-chain acyl-CoA dehydrogenase deficiency TMS Alanine aminotransferase TMS tandem mass spectrometry business 030217 neurology & neurosurgery CK creatine kinase |
| Zdroj: | Molecular Genetics and Metabolism Reports, Vol 24, Iss, Pp 100632-(2020) Molecular Genetics and Metabolism Reports |
| ISSN: | 2214-4269 |
| Popis: | 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. Highlights • Early identification by newborn screening prevents disease related complications. • Newborn screening is changing prevalence clinical and molecular heterogeneity of FAODs. • Genotype-phenotype correlation helps to achieve personalized follow-up and treatment. • Enzymatic assay may be pivotal in predicting phenotype and symptoms severity. • Diagnosis on clinical grounds is anyway important to change disease course. |
| Databáze: | OpenAIRE |
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