Inherited disorders of neurotransmitter metabolism are rare neurodevelopmental diseases presenting with movement disorders and global developmental delay. This study presents the results of the first standardized deep phenotyping approach and describes the clinical and biochemical presentation at disease onset as well as diagnostic approaches of 275 patients from the registry of the International Working Group on Neurotransmitter related Disorders. The results reveal an increased rate of prematurity, a high risk for being small for gestational age and for congenital microcephaly in some disorders. Age at diagnosis and the diagnostic delay are influenced by the diagnostic methods applied and by disease-specific symptoms. The timepoint of investigation was also a significant factor: delay to diagnosis has decreased in recent years, possibly due to novel diagnostic approaches or raised awareness. Although each disorder has a specific biochemical pattern, we observed confounding exceptions to the rule. The data provide comprehensive insights into the phenotypic spectrum of neurotransmitter disorders.

Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines / Kuseyri Hübschmann, Oya; Horvath, Gabriella; Cortès-Saladelafont, Elisenda; Yıldız, Yılmaz; Mastrangelo, Mario; Pons, Roser; Friedman, Jennifer; Mercimek-Andrews, Saadet; Wong, Suet-Na; Pearson, Toni S.; Zafeiriou, Dimitrios I.; Kulhánek, Jan; Kurian, Manju A.; López-Laso, Eduardo; Oppebøen, Mari; Kılavuz, Sebile; Wassenberg, Tessa; Goez, Helly; Scholl-Bürgi, Sabine; Porta, Francesco; Honzík, Tomáš; Santer, René; Burlina, Alberto; Sivri, H. Serap; Leuzzi, Vincenzo; Hoffmann, Georg F.; Jeltsch, Kathrin; Hübschmann, Daniel; Garbade, Sven F.; Assmann, Birgit; Fung, Cheuk-Wing; Guder, Philipp; Hong, Stacey Tay Kiat; Karall, Daniela; Kato, Mitsuhiro; Kavecan, Ivana; Koht, Jeanette Aimee; Kuster, Alice; Lücke, Thomas; Manti, Filippo; Mir, Pablo; Mühlhausen, Chris; Önenli Mungan, Halise Neslihan; Palacios, Natalia Alexandra Julia; Ramos, Joaquín Alejandro Fernández; Steel, Dora; Stevanović, Galina; Sykut-Cegielska, Jolanta; Verbeek, Marcel M.; García-Cazorla, Angeles; Opladen, Thomas. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 12:1(2021). [10.1038/s41467-021-25515-5]

Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines

Mastrangelo, Mario;Leuzzi, Vincenzo;Manti, Filippo;
2021

Abstract

Inherited disorders of neurotransmitter metabolism are rare neurodevelopmental diseases presenting with movement disorders and global developmental delay. This study presents the results of the first standardized deep phenotyping approach and describes the clinical and biochemical presentation at disease onset as well as diagnostic approaches of 275 patients from the registry of the International Working Group on Neurotransmitter related Disorders. The results reveal an increased rate of prematurity, a high risk for being small for gestational age and for congenital microcephaly in some disorders. Age at diagnosis and the diagnostic delay are influenced by the diagnostic methods applied and by disease-specific symptoms. The timepoint of investigation was also a significant factor: delay to diagnosis has decreased in recent years, possibly due to novel diagnostic approaches or raised awareness. Although each disorder has a specific biochemical pattern, we observed confounding exceptions to the rule. The data provide comprehensive insights into the phenotypic spectrum of neurotransmitter disorders.
2021
neurotransmitter disorders; dopamine; children
01 Pubblicazione su rivista::01a Articolo in rivista
Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines / Kuseyri Hübschmann, Oya; Horvath, Gabriella; Cortès-Saladelafont, Elisenda; Yıldız, Yılmaz; Mastrangelo, Mario; Pons, Roser; Friedman, Jennifer; Mercimek-Andrews, Saadet; Wong, Suet-Na; Pearson, Toni S.; Zafeiriou, Dimitrios I.; Kulhánek, Jan; Kurian, Manju A.; López-Laso, Eduardo; Oppebøen, Mari; Kılavuz, Sebile; Wassenberg, Tessa; Goez, Helly; Scholl-Bürgi, Sabine; Porta, Francesco; Honzík, Tomáš; Santer, René; Burlina, Alberto; Sivri, H. Serap; Leuzzi, Vincenzo; Hoffmann, Georg F.; Jeltsch, Kathrin; Hübschmann, Daniel; Garbade, Sven F.; Assmann, Birgit; Fung, Cheuk-Wing; Guder, Philipp; Hong, Stacey Tay Kiat; Karall, Daniela; Kato, Mitsuhiro; Kavecan, Ivana; Koht, Jeanette Aimee; Kuster, Alice; Lücke, Thomas; Manti, Filippo; Mir, Pablo; Mühlhausen, Chris; Önenli Mungan, Halise Neslihan; Palacios, Natalia Alexandra Julia; Ramos, Joaquín Alejandro Fernández; Steel, Dora; Stevanović, Galina; Sykut-Cegielska, Jolanta; Verbeek, Marcel M.; García-Cazorla, Angeles; Opladen, Thomas. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 12:1(2021). [10.1038/s41467-021-25515-5]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1569596
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