| Summary: | Metabolomics is an emerging field and requires a global approach to metabolism.
It describes how varying factors (diet, exercise, disease, etc.) influences
metabolism. A metabolomic approach can not only make it easier to detect
changes in metabolic conversion but also shed new light on mechanisms in
metabolism. Biomarkers for a given metabolic disease can easily be detected in
the urine by conventional metabolic screening tests such as Gas
Chromatography-Mass Spectrometry analysis of organic acids and Liquid
Chromatography-Tandem Mass Spectrometry analysis of acylcarnitines for
homozygote patients. With this metabolomics based approach it might become
easier to also detect heterozygote patients by grouping of the same biomarkers.
In order to see if this is possible a metabolomics based approach was used in
this study to see if heterozygotes with defects in mitochondria1 P-oxidation can be
diagnosed.
Two approaches were used. The effect of L-carnitine supplementation on Poxidation
in normal persons were studied to generate reference values.
Heterozygote members of two families with different inborn errors in their fatty
acid oxidation (Medium Chain Acyl-CoA Dehydrogenase Defect and Multiple
Acyl-CoA Dehydrogenase Defect) were diagnosed by conventional urine tests.
A linear summation technique was designed and applied to the data obtained
from the two families. The heterozygote members of both families had
significantly elevated concentration values above reference values, but not so
high as the homozygote members. Thus it can be concluded that heterozygote
patients can be detected with urine tests with the use of the newly designed
linear summation technique. Basic- and advanced acylcarnitine ratios were calculated to enhance the
differentiation between selected medications and diseases affecting β-oxidation
with varying degrees of success. The acylcarnitine ratios that were calculated are
only useful when it is already known that the disease is a defect of P-oxidation. It
nonetheless gave an indication that this approach can be useful to diagnose
heterozygote patients. === Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2007
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