Unique plasma metabolite signature for adolescents with Klinefelter syndrome reveals altered fatty acid metabolism

Conditions related to cardiometabolic disease, including metabolic syndrome and type 2 diabetes, are common among men with Klinefelter syndrome (KS). The molecular mechanisms underlying this aberrant metabolism in KS are largely unknown, although there is an assumption that chronic testosterone deficiency plays a role. This cross-sectional study compared plasma metabolites in 31 pubertal adolescent males with KS to 32 controls of similar age (14 ± 2 yrs), pubertal stage, and body mass index z-score (0.1 ± 1.2), and then between testosterone treated (n=16) and untreated males with KS. The plasma metabolome in males with KS was distinctly different from controls, with 22% of measured metabolites having a differential abundance and seven metabolites nearly completely separating KS from controls (AUC>0.9, p