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18.09.2017 | Original Article

Diagnostic approach to neurotransmitter monoamine disorders: experience from clinical, biochemical, and genetic profiles

verfasst von: Alice Kuster, Jean-Baptiste Arnoux, Magalie Barth, Delphine Lamireau, Nada Houcinat, Cyril Goizet, Bérénice Doray, Stéphanie Gobin, Manuel Schiff, Aline Cano, Daniel Amsallem, Christine Barnerias, Boris Chaumette, Marion Plaze, Abdelhamid Slama, Christine Ioos, Isabelle Desguerre, Anne-Sophie Lebre, Pascale de Lonlay, Laurence Christa, Individual contributors who contributed to this work

Erschienen in: Journal of Inherited Metabolic Disease | Ausgabe 1/2018

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Abstract

Background and aim

To improve the diagnostic work-up of patients with diverse neurological diseases, we have elaborated specific clinical and CSF neurotransmitter patterns.

Methods

Neurotransmitter determinations in CSF from 1200 patients revealed abnormal values in 228 (19%) cases. In 54/228 (24%) patients, a final diagnosis was identified.

Results

We have reported primary (30/54, 56%) and secondary (24/54, 44%) monoamine neurotransmitter disorders. For primary deficiencies, the most frequently mutated gene was DDC (n = 9), and the others included PAH with neuropsychiatric features (n = 4), PTS (n = 5), QDPR (n = 3), SR (n = 1), and TH (n = 1). We have also identified mutations in SLC6A3, FOXG1 (n = 1 of each), MTHFR (n = 3), FOLR1, and MTHFD (n = 1 of each), for dopamine transporter, neuronal development, and folate metabolism disorders, respectively. For secondary deficiencies, we have identified POLG (n = 3), ACSF3 (n = 1), NFU1, and SDHD (n = 1 of each), playing a role in mitochondrial function. Other mutated genes included: ADAR, RNASEH2B, RNASET2, SLC7A2-IT1 A/B lncRNA, and EXOSC3 involved in nuclear and cytoplasmic metabolism; RanBP2 and CASK implicated in post-traductional and scaffolding modifications; SLC6A19 regulating amino acid transport; MTM1, KCNQ2 (n = 2), and ATP1A3 playing a role in nerve cell electrophysiological state. Chromosome abnormalities, del(8)(p23)/dup(12) (p23) (n = 1), del(6)(q21) (n = 1), dup(17)(p13.3) (n = 1), and non-genetic etiologies (n = 3) were also identified.

Conclusion

We have classified the final 54 diagnoses in 11 distinctive biochemical profiles and described them through 20 clinical features. To identify the specific molecular cause of abnormal NT profiles, (targeted) genomics might be used, to improve diagnosis and allow early treatment of complex and rare neurological genetic diseases.

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Titel: Diagnostic approach to neurotransmitter monoamine disorders: experience from clinical, biochemical, and genetic profiles
verfasst von: Alice Kuster
Jean-Baptiste Arnoux
Magalie Barth
Delphine Lamireau
Nada Houcinat
Cyril Goizet
Bérénice Doray
Stéphanie Gobin
Manuel Schiff
Aline Cano
Daniel Amsallem
Christine Barnerias
Boris Chaumette
Marion Plaze
Abdelhamid Slama
Christine Ioos
Isabelle Desguerre
Anne-Sophie Lebre
Pascale de Lonlay
Laurence Christa
Individual contributors who contributed to this work
Publikationsdatum: 18.09.2017
Verlag: Springer Netherlands
Erschienen in: Journal of Inherited Metabolic Disease / Ausgabe 1/2018
Print ISSN: 0141-8955
Elektronische ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-017-0079-6

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Diagnostic approach to neurotransmitter monoamine disorders: experience from clinical, biochemical, and genetic profiles

Abstract

Background and aim

Methods

Results

Conclusion

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Abstract

Background and aim

Methods

Results

Conclusion

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