title: High prevalence of short-chain acyl-CoA dehydrogenase deficiency in the Netherlands, but no association with epilepsy of unknown origin in childhood.
abstract: Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of metabolism, most frequently associated with developmental delay and/or epilepsy. Most SCADD patients carry common SCAD-encoding gene ( ACADS) variants or these variants in combination with a rare ACADS mutation, in the Netherlands predominantly the c.1058C>T. Epilepsy in childhood often remains unexplained and patients with epilepsy related to SCADD may remain undiagnosed because studies for SCADD are often not performed. To test this hypothesis and to further estimate the extent of the Dutch SCADD population, we performed a study on blood spot samples in 131 paediatric patients with epilepsy and 909 anonymous newborns and investigated the presence of the 2 common ACADS variants and the rare c.1058C>T mutation. Overall, the 2 common ACADS variants and the rare c.1058C>T mutation were detected in either homozygous or compound heterozygous forms in 9.2% of the epilepsy and 7.5% of the reference group. A birth prevalence of SCADD with a mutation/variant genotype in the Netherlands as high as >1:1,000 was calculated. This is in contrast with the low number of patients diagnosed clinically and supports the hypothesis that SCADD is clinically irrelevant. Furthermore our study does not support an association between SCADD and epilepsy.
authors.affiliation: Department of Paediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. b.van.maldegem@gelre.nl
authors.forename: B T
authors.initials: BT
authors.lastname: van Maldegem
authors.forename: S F
authors.initials: SF
authors.lastname: Kloosterman
authors.forename: W J
authors.initials: WJ
authors.lastname: Janssen
authors.forename: P B
authors.initials: PB
authors.lastname: Augustijn
authors.forename: J H
authors.initials: JH
authors.lastname: van der Lee
authors.forename: L
authors.initials: L
authors.lastname: Ijlst
authors.forename: H R
authors.initials: HR
authors.lastname: Waterham
authors.forename: R
authors.initials: R
authors.lastname: Duran
authors.forename: R J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: F A
authors.initials: FA
authors.lastname: Wijburg
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency / Q000235:genetics; D000293:Adolescent; D044926:Butyryl-CoA Dehydrogenase / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004827:Epilepsy / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics; D009426:Netherlands / Q000453:epidemiology; D010372:Pediatrics
chemical_list: D044926:Butyryl-CoA Dehydrogenase; D042964:Acyl-CoA Dehydrogenase