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

• DOI: 10.1038/s41467-021-25515-5
• Publication Date: 2021-09-20T10:02:53Z
• Authors: Oya Kuseyri Hübsc...; Gabriella Horvath; Elisenda Cortès-S...; Yılmaz Yıldız; Mario Mastrangelo; Roser Pons; Jennifer Friedman; Saadet Mercimek-A...; Suet-Na Wong; Toni S. Pearson; Dimitrios I. Zafe...; Jan Kulhánek; Manju A. Kurian; Eduardo López-Laso; Mari Oppebøen; Sebile Kılavuz; Tessa Wassenberg; Helly Goez; Sabine Scholl-Bürgi; Francesco Porta; Tomáš Honzík; René Santer; Alberto Burlina; H. Serap Sivri; Vincenzo Leuzzi; Georg F. Hoffmann; Kathrin Jeltsch; Daniel Hübschmann; Sven F. Garbade; ; Birgit Assmann; Cheuk-Wing Fung; Philipp Guder; Stacey Tay Kiat Hong; Daniela Karall; Mitsuhiro Kato; Ivana Kavecan; Jeanette Aimee Koht; Alice Kuster; Thomas Lücke; Filippo Manti; Pablo Mir; Chris Mühlhausen; Halise Neslihan Ö...; Natalia Alexandra...; Joaquín Alejandro...; Dora Steel; Galina Stevanović; Jolanta Sykut-Ceg...; Marcel M. Verbeek; Angeles García-Ca...; Thomas Opladen
• Keywords: Biogenic Amines; Child, preschool; Biogenic amines; Embarazo; Science; Genetic diseases, inborn; Article; Infant, newborn; 03 medical and health sciences; neurotransmitter disorders; dopamine; children; Biogenic Amines/metabolism; Recién nacido; Pregnancy; Humans; 0303 health sciences; Enfermedades genéticas congénitas; Q; Femenino; Genetic Diseases, Inborn; Infant, Newborn; Infant; Radboudumc 3: Disorders of movement DCMN: Donders Center for Medical Neuroscience; Lactante; Delivery, Obstetric; 3. Good health; Phenotype; Child, Preschool; Genetic Diseases, Inborn/diagnosis; Delivery, obstetric; Female; pregnancy; Fenotipo

AbstractInherited 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.