Outcome of Patients With Inherited Neurotransmitter Disorders

Abstract

We report the outcome of 12 patients with inherited neurotransmitter disorders of monoamine, tetrahydrobiopterin and γ amino butyric acid metabolisms from a single Inherited Neurotransmitter Disorder Clinic including tyrosine hydroxylase (n=2), aromatic l-amino acid decarboxylase (n=1), 6-pyruvoyltetrahydropterin synthase, dihydropteridine reductase and succinic semialdehyde dehydrogenase deficiencies. Six patients (with 6-pyruvoyltetrahydropterin synthase, dihydropteridine reductase and tyrosine hydroxylase deficiencies) had normal neurodevelopmental outcome on treatment. Tetrahydrobiopterin loading test in newborns with positive newborn screening for phenylketonuria will identify patients with 6-pyruvoyltetrahydropterin synthase and dihydropteridine reductase deficiencies resulting in abnormal neurotransmitter synthesis in the central nervous system in the neonatal period to initiate disease-specific treatment to improve neurodevelopmental outcome.

Development of an Innovative SQL-Based Approach to Identify Potential Patients with Neurotransmitter Disorders

“…A retrospective cohort study carried out at a single centre in Canada reported a 4% prevalence of inherited NTDs in patients with global developmental delay, neonatal hypotonia, neonatal seizures, epilepsy, and movement disorders, who underwent cerebrospinal fluid (CSF) neurotransmitter measurements for diagnostic work-up [2]. Measurement of CSF neurotransmitter metabolites (e.g., homovanillic acid [HVA], 5-hydroxyindolacetic acid [5-HIAA], 3-O-methyldopa [3-OMD], tetrahydrobiopterin, biopterin, and neopterin) is used to identify disorders of catecholamine, serotonin, and biopterin metabolisms, with diagnosis confirmed by direct sequencing of candidate genes [3].…”