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
Copyright policy )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
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.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.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.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.
- University of Padua Italy
- University of Freiburg Germany
- Azienda Ospedaliera Universitaria Integrata Verona Italy
- University of Verona Italy
Enzymaktivität, FAODs, fatty acid oxidation disorders, MCADD, medium-chain acyl-CoA dehydrogenase deficiency, Medicine (General), MADD, multiple acyl-CoA dehydrogenase deficiency, TFPD, trifunctional protein deficiency, QH301-705.5, Myopathy, Enzymatic activity; Expanded newborn screening; Fatty acid oxidation defects; Hypoglycaemia; Myopathy; Synergistic heterozygosity, 610, Expanded newborn screening, DNA, Deoxyribonucleic acid, NBS, newborn screening, PCR, polymerase chain reaction, R5-920, CACTD, carnitine-acylcarnitine translocase deficiency, Fatty acid oxidation defects, CPT1/2 D, carnitine palmitoyl-CoA transferase 1/2 deficiency, CUD, carnitine uptake defect, Biology (General), SCADD, short chain acyl-CoA dehydrogenase deficiency, DBS, dried blood spots, Synergistic heterozygosity, Enzymatic activity, LCHADD, Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency, ALT, Alanine aminotransferase, NGS, next generation sequencing, Muskelkrankheit, Hypoglykämie, VLCADD, very-long-chain acyl-CoA dehydrogenase deficiency, TMS, tandem mass spectrometry, AST, Aspartate aminotransferase, Hypoglycaemia, CK, creatine kinase, Research Paper
Enzymaktivität, FAODs, fatty acid oxidation disorders, MCADD, medium-chain acyl-CoA dehydrogenase deficiency, Medicine (General), MADD, multiple acyl-CoA dehydrogenase deficiency, TFPD, trifunctional protein deficiency, QH301-705.5, Myopathy, Enzymatic activity; Expanded newborn screening; Fatty acid oxidation defects; Hypoglycaemia; Myopathy; Synergistic heterozygosity, 610, Expanded newborn screening, DNA, Deoxyribonucleic acid, NBS, newborn screening, PCR, polymerase chain reaction, R5-920, CACTD, carnitine-acylcarnitine translocase deficiency, Fatty acid oxidation defects, CPT1/2 D, carnitine palmitoyl-CoA transferase 1/2 deficiency, CUD, carnitine uptake defect, Biology (General), SCADD, short chain acyl-CoA dehydrogenase deficiency, DBS, dried blood spots, Synergistic heterozygosity, Enzymatic activity, LCHADD, Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency, ALT, Alanine aminotransferase, NGS, next generation sequencing, Muskelkrankheit, Hypoglykämie, VLCADD, very-long-chain acyl-CoA dehydrogenase deficiency, TMS, tandem mass spectrometry, AST, Aspartate aminotransferase, Hypoglycaemia, CK, creatine kinase, Research Paper
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