Decline of acute encephalopathic crises in children with glutaryl-CoA dehydrogenase deficiency identified by newborn screening in Germany.

TY - JOUR

T1 - Decline of acute encephalopathic crises in children with glutaryl-CoA dehydrogenase deficiency identified by newborn screening in Germany.

AU - Kölker, Stefan

AU - Garbade, Sven F

AU - Boy, Nikolas

AU - Maier, Esther M

AU - Meissner, Thomas

AU - Mühlhausen, Chris

AU - Hennermann, Julia B

AU - Lücke, Thomas

AU - Häberle, Johannes

AU - Baumkötter, Jochen

AU - Haller, Wolfram

AU - Muller, Edith

AU - Zschocke, Johannes

AU - Burgard, Peter

AU - Hoffmann, Georg F

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

M3 - SCORING: Zeitschriftenaufsatz

VL - 62

SP - 357

EP - 363

JO - PEDIATR RES

JF - PEDIATR RES

SN - 0031-3998

IS - 3

M1 - 3

ER -