Effect of a valine load test on plasma alpha-keto acids in Friedreich ataxia.

To test the physiological significance in vivo of our previous in vitro finding of reduced valine dehydrogenase (VDH) activity in patients with Friedreich's Ataxia, we subjected ataxic patients and controls to an oral valine load test (1.0g) and measured the levels of branched chain alpha-keto acids in the plasma for 24 hours. We demonstrated a significantly higher peak for a alpha-keto isovaleric acid in Friedreich's Ataxia and a general trend towards higher than control values in all other alpha-keto acids measured, and at all times in the experiment. These changes are compatible with the postulated defect in regulation of the activity of VDH in this illness, but because of their small amplitude, they also indicate that a VDH deficiency is not the genetic defect in Friedreich's Ataxia.