According to an article published in the journal Metabolites, the urine of patients with hereditary angioedema (HAE) might contain a distinctive set of metabolites involved in purine metabolism, riboflavin metabolism, and the tricarboxylic acid cycle, which may be involved in the pathogenesis of HAE.

The study authors recruited 34 drug-naive patients with HAE and 82 healthy controls at the Peking Union Medical College Hospital from November 2020 to September 2021. They collected urine samples from both study groups and compared the results to reveal the metabolic signature of those with HAE. Peripheral blood samples of patients with HAE were also collected with the goal of performing DNA extraction methods and comparing the metabolomics findings between those with diverse genetic mutations.

Comprehensive metabolic analysis with high-performance liquid chromatography-tandem mass spectrometry was used to characterize the urinary metabolic signatures associated with HAE. The researchers detected and quantified a total of 795 metabolites, after which a quasi-targeted metabolomics approach identified 73 significantly altered HAE metabolites, including 59 metabolites in decreased concentrations, 14 of them with considerably increased levels.

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The results showed that urinary metabolites associated with purine and riboflavin metabolism, as well as the tricarboxylic acid cycle, oxidative stress, and inflammation, were notably different in patients with HAE. Xanthine, hypoxanthine, oxypurinol, uric acid, vitamin B2 or riboflavin, isocitrate, hydrocortisone (cortisol), cortisone, succinic, and citric acid were drastically reduced compared with the results of healthy controls.

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Next, the study authors contrasted the metabolic profiles of patients with HAE carrying different mutation types but failed to identify any significant variations.

“Several pro-inflammatory cytokines and oxidative stress markers have been found to be increased in HAE patients, suggesting complex changes in biochemical pathways in HAE patients,“ Wang and Zhi concluded. “The evaluations of metabolic changes could contribute to our understanding of HAE pathogenesis and promote the screening of diagnostic biomarkers.“

HAE is an autosomal dominant, potentially life-threatening disease with diverse clinical symptoms. The metabolites associated with the condition as well as possibly useful biomarkers require further research.  


Wang X, Zhi Y. Altered urinary metabolomics in hereditary angioedema. Metabolites. Published on November 19, 2022. doi:10.3390/metabo12111140