Journal of Pediatric Neurology
DOI: 10.1055/s-0043-1778116
Shyann Hang
1
Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
,
Chitra Prasad
1
Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
2
Genetics Metabolics Program of Southwestern Ontario, Department of Pediatrics, London Health Sciences Centre, London, Ontario, Canada
,
C. Anthony Rupar
1
Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
2
Genetics Metabolics Program of Southwestern Ontario, Department of Pediatrics, London Health Sciences Centre, London, Ontario, Canada
3
Department of Pathology and Laboratory Medicine, London, Ontario, Canada
,
Richa Agnihotri
4
Department of Medicine, McMaster University, London, Ontario, Canada
,
1
Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
5
Division of Pediatric Neurosciences, Department of Pediatrics, London Health Sciences Centre, London, Ontario, Canada
› Author Affiliations
Funding The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: this work was supported by the Schulich School of Medicine and Dentistry's Summer Research Opportunities Program, the award was granted to Shyann Hang.
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Abstract
Primary pediatric neurotransmitter disorders include genetic defects of neurotransmitter metabolism that may mimic common neurological conditions in children. Our objective was to evaluate the clinical experience and outcomes of affected patients. Five patients with primary neurotransmitter defects were identified in the neurometabolic database between 2004 and 2022. Two patients with 6-pyruvoyltetrahydropterin synthase deficiency and one with pyridoxine-dependent epilepsy (PDE) presented in the neonatal period. One patient with succinic semialdehyde dehydrogenase (SSADH) deficiency and one with aromatic l-amino acid decarboxylase (AADC) deficiency presented in later life. A diagnosis of cerebral palsy was revised following biochemical confirmation of SSADH deficiency. AADC deficiency was confirmed via exome sequencing and reduced activity on enzyme assay. Late diagnosis in the latter two cases was likely due to a low index of suspicion and lack of access to diagnostic tests in the country of origin. In two children with tetrahydrobiopterin deficiency, newborn screening results and atypical clinical features prompted investigations. An early diagnosis of PDE was established based on presenting features, a high index of suspicion, the presence of an identifiable biochemical marker and molecular genetic testing. Pediatric neurotransmitter disorders can be diagnosed based on a high clinical index of suspicion, availability of biochemical markers, and molecular genetic testing. These disorders, though rare, need to be included in the differential diagnosis of common neurological presentations in children as they may be potentially treatable. Outcomes and influencing factors in the present series are discussed in comparison to published data.
Keywords
neurotransmitter disorders -
PTPS deficiency -
PDE -
SSADH deficiency -
AADC deficiency -
cerebral palsy
Electronic Databases Accessed
https://www.ncbi.nlm.nih.gov/books/NBK1116/
https://www.omim.org/
Authors' Contribution
S.H. collected the data, wrote, and provided revision to the manuscript. A.N.P. and C.P. prepared the concept of the manuscript. C.P., A.N.P., C.A.R., and R.A. provided key edits and additions to the results and discussion. All authors approved the final manuscript.
Publication History
Received: 04 July 2023
Accepted: 02 December 2023
Article published online:
16 January 2024
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