title: Decline of acute encephalopathic crises in children with glutaryl-CoA dehydrogenase deficiency identified by newborn screening in Germany.
abstract: Glutaryl-CoA dehydrogenase (GCDH) deficiency is a rare neurometabolic disorder that is considered treatable if patients are identified before the onset of acute encephalopathic crises. To allow early identification of affected individuals, tandem mass spectrometry-based newborn screening for GCDH deficiency has been started in Germany in 1999. We prospectively followed neonatally screened patients (n=38) and compared the neurologic outcome with patients from a historical cohort (n=62). In the majority of neonatally screened children, the onset of encephalopathic crises has been prevented (89%), whereas acute encephalopathic crises or progressive neurologic impairment was common in the historical cohort. Neonatal screening in combination with intensive management is effective--even assuming ascertainment bias in the historical cohort. Similar proportions of commonest mutations and biochemical phenotypes (high and low excretors) were found in neonatally screened and historical patients. However, potential predictor variables for mild clinical phenotypes are not yet known and thus a selection of these patients by newborn screening is not excluded. No patient was known to be missed by newborn screening from 1999 to 2005. In conclusion, this study confirms that newborn screening for GCDH deficiency in combination with intensive management is beneficial.
authors.affiliation: Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children's Hospital Heidelberg, D-69120 Heidelberg, Germany. Stefan.Koelker@med.uni-heidelberg.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Kölker
authors.forename: Sven F
authors.initials: SF
authors.lastname: Garbade
authors.forename: Nikolas
authors.initials: N
authors.lastname: Boy
authors.forename: Esther M
authors.initials: EM
authors.lastname: Maier
authors.forename: Thomas
authors.initials: T
authors.lastname: Meissner
authors.forename: Chris
authors.initials: C
authors.lastname: Mühlhausen
authors.forename: Julia B
authors.initials: JB
authors.lastname: Hennermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Lücke
authors.forename: Johannes
authors.initials: J
authors.lastname: Häberle
authors.forename: Jochen
authors.initials: J
authors.lastname: Baumkötter
authors.forename: Wolfram
authors.initials: W
authors.lastname: Haller
authors.forename: Edith
authors.initials: E
authors.lastname: Muller
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
authors.forename: Peter
authors.initials: P
authors.lastname: Burgard
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy; D001928:Brain Diseases, Metabolic / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy; D002648:Child; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D005858:Germany; D050770:Glutaryl-CoA Dehydrogenase / Q000172:deficiency*; D006801:Humans; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D009043:Motor Activity / Q000502:physiology; D015997:Neonatal Screening; D011446:Prospective Studies
chemical_list: D050770:Glutaryl-CoA Dehydrogenase