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The phenotypic spectrum of paediatric neurotransmitter diseases and infantile parkinsonism

  • Symposium on Neurotransmitter Disorders
  • Published:
Journal of Inherited Metabolic Disease

Summary

Paediatric neurotransmitter diseases are a group of inherited disorders attributable to a disturbance of neurotransmitter metabolism. The monoamines, catecholamines and serotonin, also called biogenic amines, are neurotransmitters with multiple roles including psychomotor function, hormone secretion, cardiovascular, respiratory and gastrointestinal control, sleep mechanisms, body temperature and pain. Given the multiple functions of monoamines, disorders of their metabolism comprise a wide spectrum of manifestations, with motor dysfunction being the most prominent clinical feature. The severity of the clinical manifestations ranges from mild to severe. Patients with severe and intermediate phenotypes may present with infantile parkinsonism that differs in a number of aspects from the parkinsonism in nigrostriatal degeneration. Analysis of monoamine metabolites and pterins in spinal fluid assists in the diagnosis of these disorders. Treatment options include tetrahydrobiopterin supplementation, l-dopa, 5-hydroxytryptophan, and medications that potentiate monoamine transmission. Response to treatment is variable.

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Abbreviations

5-HIAA:

5-hydroxyindoleacetic acid

5-HTP:

5-hydroxytryptophan

6PTP:

6-pyruvoyltetrahydropterin

AADC:

aromatic l-amino-acid decarboxylase

BH4 :

tetrahydrobiopterin

COMT:

catechol O-methyltransferase

DA:

dopamine

DBH:

dopamine β-hydroxylase

DHPR:

dihydropteridine reductase

GTPCH:

GTP cyclohydrolase

5HT:

serotonin

HVA:

homovanillic acid

MAO:

monoamine oxidase

MHPG:

3-methoxy-4-hydroxyphenylglycol

NH2 TP:

dihydroneopterin triphosphate

PCD:

pterin 4α-carbinolamine dehydratase

PNMT:

phenylethanolamine N-methyltransferase

PTPS:

6-pyruvoyltetrahydropterin synthase

qBH2:

quinonoid dihydrobiopterin

SR:

sepiapterin reductase

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Acknowledgement

The Symposium was supported in part by R13 NS 60363 from the NIH NINDS and Office of Rare Diseases (ORD), and the Johns Hopkins University School of Medicine.

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Authors and Affiliations

  1. First Department of Paediatrics, Agia Sofia Hospital, Thivon & Papadiamantopoulou, Athens, 115 27, Greece

    R. Pons

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  1. R. Pons
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Correspondence to R. Pons.

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Communicating editor: Michael Gibson

Competing interests: None declared

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Pons, R. The phenotypic spectrum of paediatric neurotransmitter diseases and infantile parkinsonism. J Inherit Metab Dis 32, 321–332 (2009). https://doi.org/10.1007/s10545-008-1007-6

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  • DOI: https://doi.org/10.1007/s10545-008-1007-6

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