Neurotransmitter (biogenic amines) Disorders

 Neurotransmitters include the catecholamines (dopamine, norepinephrine, and epinephrine) and the indoleamines (serotonin and melatonin). They are chemical messengers, which mediate, amplify, or modulate synaptic Transmission between neurons in the brain. Consequently, neurotransmitters are involved in central brain functions including control of movements and behavior, neuronal excitation and inhibition, the regulation of body temperature, pain threshold, memory, and a host of other processes. Inherited deficiencies of neurotransmitters encompass defects of neurotransmitter biosynthesis and catabolism, as well as defects of neurotransmitter transporters. They result in a wide variety of clinical signs and symptoms. This chapter will focus on primary disorders of serotonin and dopamine metabolism. Described defects are deficiencies of tyrosine hydroxylase (TH), aromatic l -amino acid decarboxylase (AADC), dopamine ß -hydroxylase (D ß H), monoamine oxidase A, as well as the hereditary dopamine transporter syndrome and the brain dopamin- serotonin vesicular transport (VMAT2) disease.  

Neurotransmitter disorders are important to recognize because early diagnosis and prompt therapeutic intervention seem to improve motor and cognitive outcome. The disease predominantly starts during infancy and early childhood. The specific clinical presentation of individual neurotransmitter diseases is determined by the type and severity of the underlying disorder. The clinical phenotype is not characteristic but can mimic that of other neurological disorders. Although a detailed clinical history and physical examination are essential, the diagnosis is almost exclusively based on the quantitative determination of neurotransmitters or their metabolites in cerebrospinal fluid (CSF). The additional determination of pterin metabolites is needed for the differentiation from deficiencies of BH 4 metabolism. Every diagnosis must be confirmed by molecular testing. The aim of treatment is to restore neurotransmitter homeostasis. Bypassing the metabolic block using levodopa/carbidopa together with dopamine agonists has led to remarkable clinical improvement in TH deficiency. In patients with AADC deficiency and with dopamine receptor deficiency, syndrome treatment options are limited and in many cases not satisfactory. Patients with DβH deficiency benefit from dihydroxyphenylserine (DOPS) administration. While patients with VMAT2 defects benefi t from treatment with a dopamine-receptor agonist, no specifi c treatment with sustained effect for MAO-A deficiency or dopamine transporter deficiency has been described.  

For AADC deficiency consensus care guidelines developed by iNTD network members can be downloaded here:


This text is an extract from “Physician´s Guide to the Diagnosis, Treatment and Follow-Up of Inherited Metabolic Diseases”, Editors: Nenad Blau, Marinus Duran, K. Michael Gibson, Carlos Dionisi-Vici, Publisher: Springer 


Opladen T, Hoffmann GF, Neurotransmitter Disorders, Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, N. Blau et al. (eds.)  


For Patients and families​


For healthcare profesionals​


For partners​   -   Login