Aims:  To investigate risk factors for metabolic syndrome in prepubertal boys with Klinefelter syndrome.

Methods:  Eighty‐nine boys with Klinefelter syndrome, ages 4–12.9 years, and 34 age‐matched control boys had height, weight, waist circumference and blood pressure measured and their parents completed a questionnaire about physical activity. The boys with Klinefelter syndrome also had measurement of lipids, fasting glucose and insulin. Insulin‐glucose homeostasis model assessment was calculated, and the boys were evaluated for childhood metabolic syndrome.

Results:  The Klinefelter syndrome and control groups were similar ages (7.5 ± 2.4 vs. 8.1 ± 2.3 years). Body mass index measurements were similar, but waist circumference was >90 percentile in 30% of boys with Klinefelter syndrome versus 21% of controls. The mean daily time spent running was 42 min less in the Klinefelter syndrome versus control groups (p < 0.01). About 37% of the boys with Klinefelter syndrome had elevated LDL cholesterol, 24% had insulin resistance, and 7% met the three criteria for diagnosis of metabolic syndrome.

Conclusions:  Truncal obesity, insulin resistance and metabolic syndrome are present in boys as young as 4–12 years with Klinefelter syndrome, and these occur in association with reduced running‐type activity.