Rapid diagnosis of glycine encephalopathy by 13C‐glycine breath test

Abstract

It is currently problematic to confirm the clinical diagnosis of glycine encephalopathy, requiring either invasive liver biopsy for enzymatic analysis of the glycine cleavage system or exhaustive mutation analysis. Because the glycine cleavage system breaks down glycine generating carbon dioxide, we suppose that the glycine cleavage system activity could be evaluated in vivo by measuring exhaled (13)CO(2) after administration of [1-(13)C]glycine. The [1-(13)C]glycine breath test was performed in 10 control subjects and 5 glycine encephalopathy patients with GLDC mutation, including 1 patient with mild glycine encephalopathy. All the patients showed lower (13)CO(2) excretion than any control subject. Not only typical GE but also atypical GE can be reliably diagnosed by the (13)C-glycine breath test. Because it is rapid, non-invasive, and requires little expertise, the breath test could be useful as a standard test for diagnosing GE.