A serum metabolomics signature of hypothermia fatalities involving arginase activity, tryptophan content, and phosphatidylcholine saturation



Hypothermia is a potentially lethal condition whose postmortem diagnosis is often complex to perform due to the absence of pathognomonic lesions and biomarkers. Our first study of human serum and urinary metabolome in hypothermia fatalities sought novel biomarkers with better diagnostic performances than those already existing.

Material and Method

Thirty-two cases of hypothermia deaths and 16 cases excluding known antemortem exposure to cold or postmortem elements suggesting hypothermia were selected. A targeted metabolomic study allowing the detection and quantitation of 188 metabolites was performed on collected serum and urine using direct flow injection (FIA) and liquid chromatography (LC) separation, both coupled to tandem mass spectrometry (MS/MS). Amino acid quantification was also carried on using an in-house LC-MS/MS method in order to replicate the results obtained with the metabolomic study.


A discriminant metabolic signature allowing a clear separation between hypothermia and control groups was obtained in the serum. This signature was characterized by increased arginase activity and fatty acid unsaturation along with decreased levels of tryptophan in hypothermia fatalities compared to controls. By contrast, no discriminant metabolic signature separating hypothermia from control fatalities was found in urines.


The serum metabolic signature of hypothermia fatalities herein observed pointed toward metabolic adaptations that likely aimed at heat production enhancement, endothelial function, and cell membrane fluidity preservation. Novel biomarkers potentially useful in a hypothermia diagnosis were also identified.

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We would like to thank Lydie Tessier and Cédric Gadras for technical support and Donnalee Perez for language editing.

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Corresponding author

Correspondence to Guillaume Rousseau.

Ethics declarations

We confirm that all cases selected for this work underwent medicolegal autopsies directed by the public prosecutor. Biochemical investigations were performed as part of investigations.

Conflict of interest

The authors declare that they have no conflict of interest.

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Results of the serum metabolomics study. (XLSX 84.1 kb)

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Results of the urine metabolomics study (XLSX 62.2 kb)

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Rousseau, G., Chao de la Barca, J.M., Rougé-Maillart, C. et al. A serum metabolomics signature of hypothermia fatalities involving arginase activity, tryptophan content, and phosphatidylcholine saturation. Int J Legal Med 133, 889–898 (2019). https://doi.org/10.1007/s00414-018-1937-y

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  • Forensic science
  • Hypothermia
  • Metabolomics
  • Serum
  • Urine
  • Biomarkers