Clayton, P;
(2019)
The effectiveness of correcting abnormal metabolic profiles.
Journal of Inherited Metabolic Disease
10.1002/jimd.12139.
(In press).
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Abstract
Inborn errors of metabolism cause disease because of accumulation of a metabolite before the blocked step or deficiency of an essential metabolite downstream of the block. Treatments can be directed at reducing the levels of a toxic metabolite or correcting a metabolite deficiency. Many disorders have been treated successfully first in a single patient because we can measure the metabolites and adjust treatment to get them as close as possible to the normal range. Examples are drawn from Komrower's description of treatment of homocystinuria and the author's trials of treatment in bile acid synthesis disorders (3β-hydroxy-Δ5 -C27 -steroid dehydrogenase deficiency and Δ4 -3-oxosteroid 5β-reductase deficiency) , neurotransmitter amine disorders (aromatic L-amino acid decarboxylase [AADC] and tyrosine hydroxylase deficiencies) and vitamin B6 disorders (pyridox(am)ine phosphate oxidase deficiency and pyridoxine-dependent epilepsy [ALDH7A1 deficiency]). Sometimes follow-up shows there are milder and more severe forms of the disease and even variable clinical manifestations but by measuring the metabolites we can adjust the treatment to get the metabolites into the normal range. Biochemical measurements are not subject to placebo effects and will also show if the disorder is improving spontaneously. The hypothesis that can then be tested for clinical outcome is whether getting metabolite(s) in a target range leads to an improvement in an outcome parameter such as abnormal liver function tests, hypokinesia, epilepsy control etc. The metabolite-guided approach to treatment is an example of personalised medicine and is a better way of determining efficacy for disorders of variable severity than a randomised controlled clinical trial. This article is protected by copyright. All rights reserved.
| Type: | Article |
|---|---|
| Title: | The effectiveness of correcting abnormal metabolic profiles |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/jimd.12139 |
| Publisher version: | https://doi.org/10.1002/jimd.12139 |
| Language: | English |
| Additional information: | © 2019 The Authors Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| Keywords: | Bile acids, effectiveness, homocystinuria, inborn errors, n=1, neurotransmitter amines, randomised controlled trials, rare disorders, treatment, vitamin B6 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10077569 |
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