Abstract
BackgroundInherited neurotransmitter disorders are primary defects of neurotransmitter metabolism. The main purpose of this retrospective cohort study was to identify prevalence of inherited neurotransmitter disorders.MethodsThis retrospective cohort study does not have inclusion criteria; rather included all patients who underwent cerebrospinal fluid (CSF) homovanillic and 5-hydroxyindol acetic acid measurements. Patients with CSF neurotransmitter investigations suggestive of an inherited neurotransmitter disorder and patients with normal or non-diagnostic CSF neurotransmitter investigations underwent direct sequencing of single gene disorders.ResultsThere were 154 patients between October 2004 and July 2013. Four patients were excluded due to their diagnosis prior to this study dates. Two major clinical feature categories of patients who underwent lumbar puncture were movement disorders or epilepsy in our institution. Twenty out of the 150 patients (13.3%) were diagnosed with a genetic disorder including inherited neurotransmitter disorders (6 patients) (dihydropteridine reductase, 6-pyruvoyl-tetrahydropterin synthase, guanosine triphosphate cyclohydrolase I, tyrosine hydroxylase, pyridoxine dependent epilepsy due to mutations in the ALDH7A1 gene and pyridoxamine-5-phosphate oxidase deficiencies) and non-neurotransmitter disorders (14 patients).ConclusionPrevalence of inherited neurotransmitter disorders was 4% in our retrospective cohort study. Eight out of the 150 patients (5.3%) had one of the treatable inherited metabolic disorders with favorable short-term neurodevelopmental outcomes, highlighting the importance of an early and specific diagnosis. Whole exome or genome sequencing might shed light to unravel underlying genetic defects of new inherited neurotransmitter disorders in near future.
Highlights
Inherited neurotransmitter disorders are primary defects of neurotransmitter metabolism
Tyrosine hydroxylase (TH) deficiency affects the synthesis of dopamine, epinephrine and norepinephrine, whereas aromatic L-amino acid decarboxylase (AADC) and tetrahydrobiopterin metabolism defects including guanosine triphosphate cyclohydrolase I (GTPCH), dihydropteridine reductase (DHPR), 6-pyruvoyltetrahydropterin synthase (PTPS), sepiapterin reductase (SR) deficiencies lead to a deficiency of serotonin in addition to deficiencies of dopamine, epinephrine and norepinephrine [1,2,3,4,5]
All patients originating from The Hospital for Sick Children, Toronto, Canada were included who had the measurement of cerebrospinal fluid (CSF) Homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) in the Medical Neurogenetic Laboratory in Atlanta
Summary
Inherited neurotransmitter disorders are primary defects of neurotransmitter metabolism. Inherited neurotransmitter disorders are primary defects of neurotransmitter metabolism and transport. They include defects of catecholamine, serotonin, biopterin, glycine, pyridoxine and gamma amino butyric acid (GABA) metabolism [1,2]. Tyrosine hydroxylase (TH) deficiency affects the synthesis of dopamine, epinephrine and norepinephrine, whereas aromatic L-amino acid decarboxylase (AADC) and tetrahydrobiopterin metabolism defects including guanosine triphosphate cyclohydrolase I (GTPCH), dihydropteridine reductase (DHPR), 6-pyruvoyltetrahydropterin synthase (PTPS), sepiapterin reductase (SR) deficiencies lead to a deficiency of serotonin in addition to deficiencies of dopamine, epinephrine and norepinephrine [1,2,3,4,5]. As the majority of inherited neurotransmitter disorders are treatable, CSF neurotransmitter measurements would be necessary to diagnose these disorders for the initiation of the disease specific treatment
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