Lil’ Brave One (Hrabriša)
Cycle 3
Pediatric Neurotransmitter Disease is an umbrella term for genetic disorders that affect the synthesis, metabolism and catabolism of neurotransmitters in children. Inborn neurotransmitters related diseases belong to the rare metabolic, potentially treatable, genetic disorders, with clinical manifestation during childhood. The clinical phenotype is not characteristic but can mimic other neurological disorders.
Last updated 04/30/2025
Clinical
Disease Class
Genetic diseases
Inherited metabolic disorder
Neurological diseases
Body Systems
Digestive
Endocrine
Metabolic
Muscular / Skeletal
Nervous / Sensory
Respiratory
Organs
Bones
Brain
Connective tissue / joints
Eyes
Heart
Intestines
Liver
Muscles
Nerves
Nose
Pituitary glands
Thyroid
Known Genetic Link
Yes, one or more genes directly cause the condition
causative_genes
ABAT
ALDH5A1
AMT
DBH
DDC
DHFR
DHPR
DNAJC12
FOLR1
GCH1
GCSH
GLDC
MAOA
PHGDH
PSAT1
PSPH
PTS
QDPR
SLC6A3
SLC6A9
SPR
TH
contributory_genes
None specified / unknown
Type of Inheritance
Autosomal dominant
Autosomal recessive
De novo
X-linked dominant
Newborn Screening
Yes, for some genes
Yes, in some states
Disease Mechanism(s)
Cofactor deficiency
Enzyme deficiency
Inherited metabolic disorder
Myelination defect
Pathogenic mutation
Protein misfolding
Receptor defect
Transport defect
Age of Onset
Adolescence (12-17)
Adulthood (age 18-64)
Early childhood (age 1+-5)
Infancy (age 0-1)
Middle childhood (6-11)
Prebirth
Average Age at Diagnosis
Adolescence (12-17)
Adulthood (age 18-64)
Early childhood (age 1+-5)
Infancy (age 0-1)
Middle childhood (6-11)
Pre-Birth
Life Expectancy
Adolescence (12-17)
Adulthood (age 18-64)
Early childhood (age 1+-5)
Elderly (age 65+)
Infancy (age 0-1)
Middle childhood (6-11)
Affected Sex(es)
Female
Intersex
Male
National Prevalence
11-50
Global Prevalence
101-1000
National Incidence
Less than 10
Global Incidence
11-50
Populations and/or ancestry with higher prevalence
Only for one subgroup of RNDs (AADC deficiency), there is a so-called founder mutation known in Taiwanese of Chinese origin, resulting in higher prevalence and incidence.
Symptoms / Phenotypes
abnormal eye morphology
abnormality of limbs
autistic behavior
behavioral changes
breathing difficulties
cardiac abnormalities
constipation
developmental delay
diarrhea
dysarthria
enlarged liver / hepatomegaly
exaggerated startle response
excessive salivation
failure to thrive
fatigue
feeding difficulties
gastroesophageal reflux
gastrointestinal disorders
hyperhidrosis
hypoglycemia
hypogonadism
hypotension
hypotonia
inappropriate crying
increased circulating prolactin concentration
microcephaly
movement disorders / ataxia / tremor
muscle weakness
nasal congestion
poor head control
seizures / epilepsy
sleep disorders
temperature instability
vision problems
Biomarkers
Diagnostic
· CSF biomarkers - 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), (2) pterins including neopterin and biopterin, 3-O-methyldopa (3-OMD), L-Dopa and 5-OH tryptophan (5-HTP), 5-methyltetrahydrofolate (5-MTHF); GABA, GBF, primapterin, serine, glycine, beta- alanine. 3OMD dry blood spot biomarker. GHB, phenylalanine. Serum glycemia, ammoniemia.
Monitoring
· HVA homovanillic acid, 5HIAA, glycine, serine, Phe, tyrosine
Prognostic
· HVA homovanillic acid
Therapeutic
· HVA, 5HIAA, glycine, serine, Phe, tyrosine, 3OMD
Existing Therapies
FDA-Approved for Symptom Relief
· methylphenidate, thioridazine, risperidone or fluoxetine Baclofen, inhibitors MAO, psychiatric drugs
FDA-Approved to Cure or Modify the Disease
· Kuvan (Sapropterin Dihydrochloride), Kebilidi (eladocagene exuparvovec-tneq, FDA approval), Upstaza (Eladocagene exuparvovec, EMA approval), L-dopa/decarboxylase inhibitor; sodium benzoate, folinic acid, pramipexole;
Off-Label Drug Use
Organizational & Research
Cell Lines
None
Cell Lines, Institution
None
Cell Lines, share
N/A
Disease Model
None
Disease Model, share
N/A
Clinical Trial Role
Not involved
Biobank, Institution
None
Center of Excellence, Institution
Universitätsklinikum Heidelberg
Center of Excellence, Involvement
Consulted
Registry
Yes, we have collaborated on a registry
Data Collected, Registry
Clinical data
Genetic data
Imaging data
Longitudinal natural history data
Medication usage
Patient-reported data
Data Entered by, Registry
Clinicians
Platform, Registry
REDCap
Natural History Study
Yes, we have collaborated on a natural history study
Data Collected, Natural History Study
Clinical endpoints (outcomes)
Genetic data
Imaging data
Medication usage
Patient-reported outcomes
Retrospective data
Platform, Natural History Study
REDCap
FDA Patient Listening Session
No
FDA Patient-Focused Drug Development (PFDD) Program
No
ICD Codes
We use an ICD-10 code capturing the family of diseases to which our disease belongs
Diagnostic Guidelines
In the process of creating formal diagnostic guidelines for publication in a peer-reviewed journal
Science Advisory Board Policies
No policies
Research Network Policies
Has CRN but no policies
Research Roadmap
We don't have a Research Roadmap
International Chapters
None
International Partners
Europe
North America