Decline of acute encephalopathic crises in children with glutaryl-CoA dehydrogenase deficiency identified by newborn screening in Germany.
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.
Kölker
Stefan
S
Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children's Hospital Heidelberg, D-69120 Heidelberg, Germany. Stefan.Koelker@med.uni-heidelberg.de
Garbade
Sven F
SF
Boy
Nikolas
N
Maier
Esther M
EM
Meissner
Thomas
T
Mühlhausen
Chris
C
Hennermann
Julia B
JB
Lücke
Thomas
T
Häberle
Johannes
J
Baumkötter
Jochen
J
Haller
Wolfram
W
Muller
Edith
E
Zschocke
Johannes
J
Burgard
Peter
P
Hoffmann
Georg F
GF
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
D050770:Glutaryl-CoA Dehydrogenase