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

• 12 August 2024

ARTICLE
Insights into the expanding phenotypic spectrum of
inherited disorders of biogenic amines
Oya Kuseyri Hübschmann 1, Gabriella Horvath2, Elisenda Cortès-Saladelafont3,4, Yılmaz Yıldız 5,
Mario Mastrangelo6, Roser Pons7, Jennifer Friedman8, Saadet Mercimek-Andrews 9, Suet-Na Wong10,
Toni S. Pearson 11, Dimitrios I. Zafeiriou12, Jan Kulhánek13, Manju A. Kurian14, Eduardo López-Laso15,
Mari Oppebøen16, Sebile Kılavuz17, Tessa Wassenberg18,19, Helly Goez20, Sabine Scholl-Bürgi21,
Francesco Porta22, Tomáš Honzík13, René Santer23, Alberto Burlina24, H. Serap Sivri 5, Vincenzo Leuzzi6,
Georg F. Hoffmann1, Kathrin Jeltsch1, Daniel Hübschmann25,26,27,28, Sven F. Garbade 29, iNTD Registry Study
Group*, Angeles García-Cazorla3 & Thomas Opladen 1✉
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.
https://doi.org/10.1038/s41467-021-25515-5 OPEN
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