Elevated Urinary Globotriaosylceramide Suggested as New Heart Disease Biomarker

Elevated Gb3 had not been connected previously to non-Fabry heart conditions.

Investigators at Baylor Research Institute (Dallas, TX, USA) were screening heart disease patients for Fabry disease when they found that even in the absence of Fabry many of the patients had elevated Gb3 in their urine. They had screened 1,421 consecutive patients with common forms of heart disease for Fabry disease by measuring urinary Gb3 in whole urine using tandem mass spectrometry. They also determined GLA activity in dried blood spots, and they looked for GLA mutations by parallel sequencing of the whole gene (exons and introns) in pooled genomic DNA samples followed by Sanger sequencing verification.

They reported finding GLA variants in 13 patients. In the 1,408 patients without GLA mutations, urinary Gb3 levels were significantly higher in heart disease patients compared to 116 apparently healthy controls.

Urinary lipid profiling showed that levels of five other lipids could distinguish between urine of seven patients with Fabry disease and six other heart disease patients with elevated urinary Gb3. Sphingomyelin and Gb3 levels were abnormal in the left ventricular wall of patients with ischemic heart failure. Elevated levels of urinary Gb3 were independently associated with increased risk of death in the average follow-up period of 17 months.

“To our surprise, we noticed after a few months that some heart disease patients who did not have Fabry disease did have elevated Gb3 in the urine,” said senior author Dr. Raphael Schiffmann, medical director of the institute of metabolic disease at the Baylor Research Institute. “Simultaneously, we also found that some of those patients had died in the short interval that had passed since we had last seen them for this screening study. This was a very surprising, yet encouraging, discovery, given the fact that Gb3 elevation was, until now, thought to be the exclusive hallmark of Fabry disease. Remarkably, this biomarker is significantly different from existing ones and could be of great significance for the future study of heart disease.”

The study was published in the February 4, 2014, online edition of the Journal of the American Heart Association.

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