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  • Review Article
  • Published:

Monoamine neurotransmitter disorders—clinical advances and future perspectives

Nature Reviews Neurology volume 11, pages 567–584 (2015)Cite this article

Subjects

Key Points

  • Monoamine neurotransmitter disorders are under-recognized and often misdiagnosed, as many mimic cerebral palsy and other neurological disorders

  • 'Red flag' symptoms of monoamine neurotransmitter disorders include diurnal variation of symptoms, a mixed movement disorder, autonomic disturbance, involvement of the eyes (ptosis, oculogyric crisis) and levodopa responsiveness

  • Many monoamine neurotransmitter disorders are amenable to treatment; appropriate therapy is curative in some disorders

  • Analysis of cerebrospinal fluid neurotransmitter levels aids identification of the specific monoamine pathway defect and is vital for accurate diagnosis of most primary neurotransmitter disorders and selection of appropriate disease-specific pharmacotherapy

  • Research in the past few years has identified novel monoamine neurotransmitter disorders that involve defects in dopamine transport and monoamine vesicle packaging

  • Discoveries of novel genetic defects and biomarkers in monoamine neurotransmitter disorders, together with novel disease models, will improve our understanding of pathophysiological mechanisms and facilitate the development of new treatments

Abstract

The monoamine neurotransmitter disorders are important genetic syndromes that cause disturbances in catecholamine (dopamine, noradrenaline and adrenaline) and serotonin homeostasis. These disorders result in aberrant monoamine synthesis, metabolism and transport. The clinical phenotypes are predominantly neurological, and symptoms resemble other childhood neurological disorders, such as dystonic or dyskinetic cerebral palsy, hypoxic ischaemic encephalopathy and movement disorders. As a consequence, monoamine neurotransmitter disorders are under-recognized and often misdiagnosed. The diagnosis of monoamine neurotransmitter disorders requires detailed clinical assessment, cerebrospinal fluid neurotransmitter analysis and further supportive diagnostic investigations. Prompt and accurate diagnosis of neurotransmitter disorders is paramount, as many are responsive to treatment. The treatment is usually mechanism-based, with the aim to reverse disturbances of monoamine synthesis and/or metabolism. Therapeutic intervention can lead to complete resolution of motor symptoms in some conditions, and considerably improve quality of life in others. In this Review, we discuss the clinical features, diagnosis and management of monoamine neurotransmitter disorders, and consider novel concepts, the latest advances in research and future prospects for therapy.

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Figure 1: Overview of primary and secondary monoamine neurotransmitter disorders.
Figure 2: Monoamine synthesis and metabolism in neurons.
Figure 3: A guide to the clinical diagnosis of neurotransmitter disorders.
Figure 4: Neurotransmitter profiles, metabolite profiles and other diagnostic investigations in neurotransmitter disorders.

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Acknowledgements

M.A.K. is funded by a Wellcome Intermediate Clinical Fellowship (WT098524MA) and receives funding from the Rosetrees Trust and the Gracious Heart Charity Foundation. J.N. is funded by a Medical Research Council Clinical Research Training Fellowship (MR/K02342X/1). M.A.K. and J.N. are both funded by Great Ormond Street Hospital Children's Charities. A.P. receives funding from Actelion to study undiagnosed neurodegenerative disorders, the NBIA Disorders Association and Child Brain Research. None of the authors received funding for the preparation of this manuscript.

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  1. Institute of Child Health, University College London, 30 Guilford Street, WC1N 1EH, London, UK

    Joanne Ng, Apostolos Papandreou & Manju A. Kurian

  2. Neurometabolic Unit, National Hospital, Queen Square, WC1N 3BG, London, UK

    Simon J. Heales

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  1. Joanne Ng
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  2. Apostolos Papandreou
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J.N. wrote the first draft and provided substantial input into revision of the manuscript. A.P. prepared tables and figures and contributed to revision of the manuscript. S.J.H. contributed to the critique of the manuscript and figures. M.A.K. provided substantial input into the manuscript concept, design, content and revision of each draft.

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Correspondence to Manju A. Kurian.

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Ng, J., Papandreou, A., Heales, S. et al. Monoamine neurotransmitter disorders—clinical advances and future perspectives. Nat Rev Neurol 11, 567–584 (2015). https://doi.org/10.1038/nrneurol.2015.172

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