iNTD registry
Research type
Research Study
Full title
International Network on Neurotransmitter related Disorders Registry
IRAS ID
174905
Contact name
Manju Kurian
Contact email
Sponsor organisation
Great Ormond Street for Children NHS Foundation Trust
Duration of Study in the UK
10 years, 0 months, 1 days
Research summary
Neurotransmitters are a group of chemical messengers that enable communication between the neurons in the synaptic cleft. Neurotransmitters include catecholamines (dopamine, norepinephrine and epinephrine), amino acids (serine, glycine, GABA) and serotonin. Neurotransmitter-related disorders are a caused by a disturbance in the biosynthesis, transport, metabolism and degradation of dopamine, norepinephrine, epinephrine, and serotonin. Brain neurotransmission is an essential process for neuronal differentiation, neuronal growth and the development of interneuronal circuit.
Neurotransmitter-related disorders are rare, with approximately 1,000 patients reported to date. Patients typically present in early childhood with often progressive neurological symptoms, such as developmental delay, hypotonia, extrapyramidal movement disorders, epilepsy and oculogyric crisis. The clinical presentation often mimics other paediatric neurological disorders and is, therefore, frequently misdiagnosed.
Early accurate diagnosis is paramount, as many neurotransmitter disorders are amenable to treatment. A minority of patients can be identified by new-born screening due to elevated blood phenylalanine level. For all others, diagnosis is made through clinical assessment and appropriate investigations, including biochemical analysis of neurotransmitters in the cerebrospinal fluid. This may be followed by specific enzyme analysis and genetic testing, if available.
Some neurotransmitters disorders are treatable. Treatment strategies focus on the correction of the deficiency by replacement of monoamine precursors, the use of monoamine analogues, inhibition of degradation, and the addition of enzyme cofactors to promote monoamine production. For many disorders, an early diagnosis appears to have a positive impact on the disease course.
Since the clinical presentation is often unspecific and mimics other neurological disorders, diagnosis is often delayed. To date, there are no evidence-based guidelines for standardised diagnostic procedures or the different treatment approaches. The principal aim of the iNTD study is to establish the first international patient registry for neurotransmitter related disorders. This registry will enable detailed analysis of the natural course of the disease, the diagnostic approaches and current therapy strategies.
REC name
London - Camden & Kings Cross Research Ethics Committee
REC reference
18/LO/1253
Date of REC Opinion
3 Apr 2019
REC opinion
Further Information Favourable Opinion