Metabolomic Approach for Diagnosis of Inborn Errors of Metabolism (IEMs) using Mass Spectrometry
Usha Dave,
Director,
MILS International India
Human Metabolomics is the latest state of the art analytical technology to monitor and discover metabolic changes in subjects related to disease status or in response to a medical or external intervention. Metabolic profiling is referred to the study of a group of metabolites associated with a particular pathway & thus global metabolomic alterations represent changes in the phenotype and molecular physiology. Its application in early diagnosis & treatment are significant for patients with IEMs. The clinical presentations are variable, non-specific & often overlapping posing a challenge to the doctor because routine laboratory tests do not indicate the aetiology of the IEM disorder.
Most IEMs cause severe pathological sequel, such as mental retardation, sudden infantile death or other irreversible mental/motor disabilities & hence early detection is important.
The mass spectrometry offers a precise & comprehensive metabolic profiling by detecting enzyme dysfunction useful in screening & differential diagnosis of IEM. The lack of coenzymes or activators, the post-translational modification defects & subcellular abnormalities are also indicated by metabolomes. The non-invasive urinary GC/MS analysis of urease treatment followed by derivatization of compounds can be used to detect simultaneously more than 140 metabolic conditions, involving IEM disorders of amino, organic & fatty acids, sugars, & nucleic acids. The Tandem mass spectrometry (TMS) offers Newborn Screening platform for common preventable IEMs which is further confirmed by GC/MS. The specific biomarkers for an individual IEM with their characteristic m/z ions during fragmentation helps in further confirming the diagnosis. In this talk, few IEMs such as MMA, MSUD, GA type-I, Beta-Ketothiolase deficiency, Canavan Disease etc. will be described. In conclusion, metabolomics has great potential to impact clinical health practices by providing reliable diagnosis which complement the genomic and proteomic pr
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