Impact of newborn screening for very-long-chain acyl-CoA dehydrogenase deficiency on genetic, enzymatic, and clinical outcomes.

Autor: Bleeker JC; Department of Metabolic Diseases, Dutch Fatty Acid Oxidation Expertise Center, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Kok IL; Department of Metabolic Diseases, Dutch Fatty Acid Oxidation Expertise Center, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.; Department of Internal Medicine and Dermatology, Dietetics, University Medical Center Utrecht, Utrecht, The Netherlands., Ferdinandusse S; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., van der Pol WL; Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, Spieren voor Spieren Kindercentrum, University Medical Center Utrecht, Utrecht, The Netherlands., Cuppen I; Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, Spieren voor Spieren Kindercentrum, University Medical Center Utrecht, Utrecht, The Netherlands., Bosch AM; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Langeveld M; Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Derks TGJ; Section of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Williams M; Center for Lysosomal and Metabolic Disorders, Department of Pediatrics, Sophia Children's Hospital EMC, Rotterdam, The Netherlands., de Vries M; Department of Pediatrics, Radboud University Medical Center, Nijmegen, The Netherlands., Mulder MF; Department of Pediatrics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Gozalbo ER; Department of Pediatrics and Clinical Genomics, Maastricht University Medical Center, Maastricht, The Netherlands., de Sain-van der Velden MGM; Department of Medical Genetics, Section Metabolic Diagnostics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands., Rennings AJ; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Schielen PJCI; National Institute for Public Health and the Environment (RIVM), Reference Laboratory for Pre- and Neonatal Screening, Bilthoven, The Netherlands., Dekkers E; National Institute for Public Health and the Environment (RIVM), Reference Laboratory for Pre- and Neonatal Screening, Bilthoven, The Netherlands., Houtkooper RH; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Waterham HR; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Pras-Raves ML; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Department of Medical Genetics, Section Metabolic Diagnostics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands., Wanders RJA; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., van Hasselt PM; Department of Metabolic Diseases, Dutch Fatty Acid Oxidation Expertise Center, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands., Schoenmakers M; Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, Spieren voor Spieren Kindercentrum, University Medical Center Utrecht, Utrecht, The Netherlands., Wijburg FA; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Visser G; Department of Metabolic Diseases, Dutch Fatty Acid Oxidation Expertise Center, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Journal of inherited metabolic disease [J Inherit Metab Dis] 2019 May; Vol. 42 (3), pp. 414-423. Date of Electronic Publication: 2019 Apr 08.
DOI: 10.1002/jimd.12075
Abstrakt: Most infants with very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) identified by newborn screening (NBS) are asymptomatic at the time of diagnosis and remain asymptomatic. If this outcome is due to prompt diagnosis and initiation of therapy, or because of identification of individuals with biochemical abnormalities who will never develop symptoms, is unclear. Therefore, a 10-year longitudinal national cohort study of genetically confirmed VLCADD patients born before and after introduction of NBS was conducted. Main outcome measures were clinical outcome parameters, acyl-CoA dehydrogenase very long chain gene analysis, VLCAD activity, and overall capacity of long-chain fatty acid oxidation (LC-FAO flux) in lymphocytes and cultured skin fibroblasts. Median VLCAD activity in lymphocytes of 54 patients, 21 diagnosed pre-NBS and 33 by NBS was, respectively, 5.4% (95% confidence interval [CI]: 4.0-8.3) and 12.6% (95% CI: 10.7-17.7; P < 0.001) of the reference mean. The median LC-FAO flux was 33.2% (95% CI: 22.8-48.3) and 41% (95% CI: 40.8-68; P < 0.05) of the control mean, respectively. Clinical characteristics in 23 pre-NBS and 37 NBS patients revealed hypoglycemic events in 12 vs 2 patients, cardiomyopathy in 5 vs 4 patients and myopathy in 14 vs 3 patients. All patients with LC-FAO flux <10% developed symptoms. Of the patients with LC-FAO flux >10% 7 out of 12 diagnosed pre-NBS vs none by NBS experienced hypoglycemic events. NBS has a clear beneficial effect on the prevention of hypoglycemic events in patients with some residual enzyme activity, but does not prevent hypoglycemia nor cardiac complications in patients with very low residual enzyme activity. The effect of NBS on prevalence and prevention of myopathy-related complications remains unclear.
(© 2019 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)
Databáze: MEDLINE
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