Neurotransmitters are a group of molecules responsible for the communication between neurons. Chemically, they can be amino acids, peptides, purines, and monoamines or biogenic amines. They are stored in the synaptic vesicles and are released after a nerve impulse, triggering an inhibitory or excitatory effect depending on the nature of the neurotransmitter or on the receptor type.
In rare cases, a malfunction of genes involved in the biosynthesis or in the degradation of the neurotransmitters can provoke rare metabolic diseases, whose incidence in the population is difficult to calculate correctly. So far, just 1500 cases have been described in scientific literature.
The relatively more spread neurotransmitter disorders are the ones related to the malfunction of monoamines and tetrahydrobiopterin (BH4). BH4 is the cofactor of various enzymes that play a fundamental role in the biosynthesis of the neurotransmitters dopamine and serotonin. The disorders related to BH4 deficiency range from mild symptoms to lethal encephalopathies. Other known rare neurometabolic disorders are related to folate transport, gamma-amino butyric acid (GABA) catabolism, serine metabolism, and glycine degradation.
The onset of this kind of neurometabolic disorders often occurs during the first months or years of life. Unfortunately, it is extremely hard to reach a correct diagnosis, mostly depending on the personal experience of the physician and because of the few information available on such disorders. Moreover, clinical symptoms are non-specific, so that it takes a lot of time and many wrong diagnoses to recognize the real nature of the disorders. Thus, the loss of time may lead to irreversible worsening of patient’s conditions and increases the costs for the health care system.
In order to overcome these problems and to give patients an earlier access to the therapies, in 2013 a group of medical experts from the University Hospital Heidelberg (Germany), the Hospital Sant Joan de Déu in Barcelona (Spain) and the Great Ormond Street Hospital in London (United Kingdom), created the International Working Group on Neurotransmitter Related Disorders (iNTD), http://www.intd-online.org. The steering committee is formed by Thomas Opladen, Àngels Garcia-Cazorla and Manju Kurian, from the mentioned German, Spanish and English hospitals, respectively.
The iNTD wants to establish an international network with the aim of improving the scientific knowledge, easing the availability of clinical data, quickening the achievement of correct diagnosis, and promoting the health care of the patients that suffer neurotransmitter disorders.
So far, iNTD is collaborating with 43 project partners from 24 countries, and in 2015 has set up a registry of patients approved by an ethics committee, and filled after the informed consent of the patients, or their representatives. To date, there are 95 patients in the registry, a number constantly increasing: the next goal is to include more than 250 patients. The patient registry, together with a deep literature search, will help to redact guidelines for a correct diagnosis and treatment of neurotransmitter disorders
It is important to notice that there is a great discrepancy between the age at which a patient receive a correct diagnosis and the age at which the first symptoms appear. This discrepancy is even greater if it is considered that most of the symptoms related to these disorders start in the first months of patient’s life. So, it can be easily understood how an early diagnosis would be essential to give the patients a rapid access to the appropriate therapies when they are available. Additionally, the network aims to develop clinical guidelines in well-defined disorders (or group of diseases) in order to increase awareness between professionals and provide an excellent care of patients
iNTD has been founded with the aim of creating a worldwide network and patient registry for rare neurometabolic disorders. It treats to give a wide access to the information necessary to obtain an early diagnosis to improve the health care of the patients. Moreover, it promotes the spread of the scientific knowledge across the medical community.
Opladen T. et al The International Working Group on Neurotransmitter related Disorders (iNTD): A worldwide research project focused on primary and secondary neurotransmitter disorders. Molecular Genetics and Metabolism Reports 9 (2016) 61–66.
The elaboration of this post has been financed by the project PI15/01082, as a part of the National Plan of I+D+I and co-financed by the ISCIII – General Deputy Direction for Evaluation and Development of Health Research – and the European Regional Development Fund (ERDF).