Diagnostic contribution of metabolic workup for neonatal inherited metabolic disorders in the absence of expanded newborn screening

Abstract Inherited metabolic disorders (IMDs) in neonates are a diagnostic and therapeutic challenge for the neonatologist, with the priority being to rapidly flag the treatable diseases. The objective of this study was to evaluate the contribution of targeted metabolic testing for diagnosing suspec...

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Autores principales:	Alexandra Bower, Apolline Imbard, Jean-François Benoist, Samia Pichard, Odile Rigal, Olivier Baud, Manuel Schiff
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/54afcfc27f9e45b38ef162f66472e7b3
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spelling	oai:doaj.org-article:54afcfc27f9e45b38ef162f66472e7b32021-12-02T15:08:21ZDiagnostic contribution of metabolic workup for neonatal inherited metabolic disorders in the absence of expanded newborn screening10.1038/s41598-019-50518-02045-2322https://doaj.org/article/54afcfc27f9e45b38ef162f66472e7b32019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50518-0https://doaj.org/toc/2045-2322Abstract Inherited metabolic disorders (IMDs) in neonates are a diagnostic and therapeutic challenge for the neonatologist, with the priority being to rapidly flag the treatable diseases. The objective of this study was to evaluate the contribution of targeted metabolic testing for diagnosing suspected IMDs on the basis of suggestive clinical setting or family history in neonates. We conducted an observational study over five years, from January 1st, 2010 to December 31, 2014 in the neonatal intensive care unit (NICU) at Robert Debré University Hospital, Paris, France. We assessed the number of neonates for whom a metabolic testing was performed, the indication for each metabolic test and the diagnostic yield of this selected metabolic workup for diagnosing an IMD. Metabolic testing comprised at least one of the following testings: plasma, urine or cerebrospinal fluid amino acids, urine organic acids, plasma acylcarnitine profile, and urine mucopolysaccharides and oligosaccharides. 11,301 neonates were admitted at the neonatal ICU during the study period. One hundred and ninety six neonates underwent metabolic testing. Eleven cases of IMDs were diagnosed. This diagnostic approach allowed the diagnosis, treatment and survival of 4 neonates (maple syrup urine disease, propionic acidemia, carnitine-acylcarnitine translocase deficiency and type 1 tyrosinemia). In total, metabolic testing was performed for 1.7% of the total number of neonates admitted in the NICU over the study period. These included 23% finally unaffected neonates with transient abnormalities, 5.6% neonates suffering from an identified IMD, 45.4% neonates suffering from a non-metabolic identified disease and 26% neonates with chronic abnormalities but for whom no final causal diagnosis could be made. In conclusion, as expected, such a metabolic targeted workup allowed the diagnosis of classical neonatal onset IMDs in symptomatic newborns. However, this workup remained normal or unspecific for 94.4% of the tested patients. It allowed excluding an IMD in 68.4% of the tested neonates. In spite of the high rate of normal results, such a strategy seems acceptable due to the severity of the symptoms and the need for immediate treatment when available in neonatal IMDs. However, its cost-effectiveness remains low especially in a clinically targeted population in a country where newborn screening is still unavailable for IMDs except for phenylketonuria in 2019.Alexandra BowerApolline ImbardJean-François BenoistSamia PichardOdile RigalOlivier BaudManuel SchiffNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alexandra Bower Apolline Imbard Jean-François Benoist Samia Pichard Odile Rigal Olivier Baud Manuel Schiff Diagnostic contribution of metabolic workup for neonatal inherited metabolic disorders in the absence of expanded newborn screening
description	Abstract Inherited metabolic disorders (IMDs) in neonates are a diagnostic and therapeutic challenge for the neonatologist, with the priority being to rapidly flag the treatable diseases. The objective of this study was to evaluate the contribution of targeted metabolic testing for diagnosing suspected IMDs on the basis of suggestive clinical setting or family history in neonates. We conducted an observational study over five years, from January 1st, 2010 to December 31, 2014 in the neonatal intensive care unit (NICU) at Robert Debré University Hospital, Paris, France. We assessed the number of neonates for whom a metabolic testing was performed, the indication for each metabolic test and the diagnostic yield of this selected metabolic workup for diagnosing an IMD. Metabolic testing comprised at least one of the following testings: plasma, urine or cerebrospinal fluid amino acids, urine organic acids, plasma acylcarnitine profile, and urine mucopolysaccharides and oligosaccharides. 11,301 neonates were admitted at the neonatal ICU during the study period. One hundred and ninety six neonates underwent metabolic testing. Eleven cases of IMDs were diagnosed. This diagnostic approach allowed the diagnosis, treatment and survival of 4 neonates (maple syrup urine disease, propionic acidemia, carnitine-acylcarnitine translocase deficiency and type 1 tyrosinemia). In total, metabolic testing was performed for 1.7% of the total number of neonates admitted in the NICU over the study period. These included 23% finally unaffected neonates with transient abnormalities, 5.6% neonates suffering from an identified IMD, 45.4% neonates suffering from a non-metabolic identified disease and 26% neonates with chronic abnormalities but for whom no final causal diagnosis could be made. In conclusion, as expected, such a metabolic targeted workup allowed the diagnosis of classical neonatal onset IMDs in symptomatic newborns. However, this workup remained normal or unspecific for 94.4% of the tested patients. It allowed excluding an IMD in 68.4% of the tested neonates. In spite of the high rate of normal results, such a strategy seems acceptable due to the severity of the symptoms and the need for immediate treatment when available in neonatal IMDs. However, its cost-effectiveness remains low especially in a clinically targeted population in a country where newborn screening is still unavailable for IMDs except for phenylketonuria in 2019.
format	article
author	Alexandra Bower Apolline Imbard Jean-François Benoist Samia Pichard Odile Rigal Olivier Baud Manuel Schiff
author_facet	Alexandra Bower Apolline Imbard Jean-François Benoist Samia Pichard Odile Rigal Olivier Baud Manuel Schiff
author_sort	Alexandra Bower
title	Diagnostic contribution of metabolic workup for neonatal inherited metabolic disorders in the absence of expanded newborn screening
title_short	Diagnostic contribution of metabolic workup for neonatal inherited metabolic disorders in the absence of expanded newborn screening
title_full	Diagnostic contribution of metabolic workup for neonatal inherited metabolic disorders in the absence of expanded newborn screening
title_fullStr	Diagnostic contribution of metabolic workup for neonatal inherited metabolic disorders in the absence of expanded newborn screening
title_full_unstemmed	Diagnostic contribution of metabolic workup for neonatal inherited metabolic disorders in the absence of expanded newborn screening
title_sort	diagnostic contribution of metabolic workup for neonatal inherited metabolic disorders in the absence of expanded newborn screening
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/54afcfc27f9e45b38ef162f66472e7b3
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Diagnostic contribution of metabolic workup for neonatal inherited metabolic disorders in the absence of expanded newborn screening

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