An Outbreak of Crayfish-Related Haff Disease in the Jiangsu Province of China: A Focus on the Metabolites

Background: Haff disease is a rare syndrome of unexplained myalgia and rhabdomyolysis occurring within 24 h of consumption of cooked fish or crustaceans, and the etiology remains unknown. Herein, we implemented a metabolomics strategy to investigate Haff disease-induced metabolite disorders. Methods: This Single, tertiary, academic medical center and Laboratory investigation included 73 crayfish-induced Haff disease-diagnosed case-patients and 73 non-crayfish diners. The serum metabolites of Haff disease patients (n = 60) were detected and analyzed with gas chromatography-mass spectrometry. The spectrum was deconvoluted, aligned, and identified using MS DIAL, equipped with FiehnLib. The data matrix was processed via univariate and multivariate analyses for the selection of metabolites with variable importance in projection values >1 and the t-test (p-value < 0.05). Results: In the case-patients, the concentrations of 20 metabolites were significantly increased and those of 6 metabolites decreased. The metabolic pathway analysis was analyzed with the MetaMapp program and visualized on CytoScape. Intriguingly, there was an enormous increase in the serum concentration of myristoleic acid in patients with Haff disease, indicating that myristoleic acid might be a key metabolite of Haff disease and a potential biomarker for crayfish or other seafood-related Haff disease. A further understanding of this disease would allow for the improved management of future disease outbreaks. Conclusions: The metabolites in the serum of the Haff disease patients was significantly disturbed, and some of which may be benefit for the diagnosis of this rare disease. Funding Statement: This work has been supported by the National Natural Science Foundation of China (81470150), the program for key diseases by the Jiangsu Province Science and Technology Department (BL2014088), and the National Natural Science Foundation of Jiangsu Province (BK20171490) Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the (Local) Ethics Committee at the Institute of the First Affiliated Hospital of Nanjing Medical University and the investigation was performed according to the ethical guidelines in Document No. 2018-SR-151.