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Title: Vitamin B6 and serotonin metabolism in neurological disorders of childhood
Author: Footitt, E. J.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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Pyridoxal 5’-phosphate (PLP) is the active form of vitamin B6 in man where it functions as a cofactor for more than 140 enzyme catalysed reactions. Several inherited diseases characterised by seizures have been described which result in an intracellular deficiency of PLP; laboratory measurement of B6 forms an important element in the diagnosis and monitoring of these disorders. A review of PLP measured by HPLC in CSF from patients with neurological disorders showed that variance is greater than indicated by previous studies and the age-related reference limit was revised. This thesis also describes the metabolic disorders that may lead to PLP depletion and examines the relationship of CSF PLP to sulphite accumulation, medications and seizures in patient groups. B6 exists as six different vitamers and is catabolised to 4-pyridoxic acid for urinary excretion. An LC-MS/MS method was developed which could measure all vitameric forms in plasma. Its application to children with B6 responsive seizure disorders showed that patients with inborn errors of metabolism have characteristic B6 profiles which allow them to be differentiated from each other and control populations. PLP is the cofactor for aromatic L-amino acid decarboxylase (AADC) which catalyses the final step in serotonin biosynthesis. This thesis tested the hypothesis that hyperserotonaemia observed in some patients with autism is related to an abnormality in this pathway by investigating the relationship between plasma B6 vitamers, AADC activity and whole blood serotonin in a group of patients and controls. Plasma AADC activity was significantly reduced in autistic subjects; this is considered in the context of current biochemical and molecular understanding and its possible relevance to disease mechanisms is discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available