Scripps Research Logo

News Release

Mass Spectrometry Metabolomics Unveils Unique Markers for Childhood Disorders

Findings Could Lead to More Accurate Clinical Diagnosis and Evaluation

LA JOLLA, CA, October 30, 2007—For the first time, scientists at The Scripps Research Institute have applied untargeted mass spectrometry-based metabolomics to uncover a number of unique molecular markers in two inherited childhood metabolic disorders. This new method could prove useful in diagnosis and patient clinical evaluation.

The study was published online October 19 by the journal Clinical Chemistry.

The study looked for significantly different molecular features in human plasma samples from patients and in samples from healthy individuals. Of the 3,500 features measured, the study was able to identify a single leading candidate as the best biomarker for methylmalonic acidemia (an inherited disorder in which the body is unable to adequately metabolize certain proteins and lipids) and propionic academia (another inherited metabolic disorder that leads to an abnormal buildup of organic acids). Effects of both methylmalonic acidemia and propionic academia usually appear in early infancy.

"Our proof-of-concept study is the first example of using global metabolomics to validate a disease biomarker and to identify other metabolites associated with the disease," said Gary Siuzdak, Scripps Research associate professor and director of the Scripps Research Center for Mass Spectrometry. "This technique should ultimately provide a better understanding of the fundamental biochemistry of these two related diseases, and could have a significant impact on how clinicians diagnose and eventually treat their young patients."

Global or untargeted metabolomics seeks to gather information on as many metabolites as possible in a given biological system. Metabolites, the products of an organism's metabolic processes are the "chemical fingerprints" that specific cellular processes leave behind. A profile of a cell's metabolites, the end products of an organism's gene expression, can give scientists a snapshot of the physiology of that cell.

In the study, the scientists used XCMS, open source software that can identify and assess metabolite features that show significant differences between sample groups, and the online metabolite database, METLIN, to help identify and compare metabolites.

"Starting out, our hypothesis was that a metabolomics study would reveal additional differences between disease and normal plasma, and give us a far more complete biochemical profile," Siuzdak said. "By applying this new toolbox of mass spectrometry methods to clinical chemistry, our results show that we have the potential to broaden our understanding of disease biochemistry, identify new biomarkers, and provide finer disease categorization and treatment."

Propionyl carnitine, a key amino acid produced by the body to metabolize lipids into energy, was identified as the best biomarker; levels of propionyl carnitine are increased substantially in both diseases. In addition, five other acylcarnitine metabolites showed significant differences between plasma samples from patients and healthy individuals; the enzyme butyrobetaine (gamma), which is responsible for the biosynthesis of propionyl carnitine, was increased in a subset of patients.

"Our study uncovered a substantial number of metabolites that do not appear in any public database and that still remain unidentified," Siuzdak said. "Many of them varied significantly between healthy patients, as well as between those with methylmalonic acidemia and propionic academia. This underscores the complex metabolic effects that can result from the defect in a single enzyme."

Access to XCMS software and the METLIN Metabolite Database are available through the Scripps Center for Mass Spectrometry:

Other authors of the study, Metabolomics Identifies Perturbations in Human Disorders of Propionate Metabolism, are William R. Wikoff of The Scripps Research Institute; and Jon A. Gangoiti and Bruce A. Barshop of the University of California San Diego. See Clinical Chemistry at

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine
development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development.
Currently operating from temporary facilities in Jupiter, Scripps Florida will move to its permanent campus in 2009.

For more information contact:
Office of Communications
10550 North Torrey Pines Road
La Jolla, California 92037