Objective To study the effectiveness of dimethylglycine (DMG) on oxygen consumption (VO 2 ) in children with Saguenay-Lac-Saint-Jean cytochrome-c oxidase (SLSJ-COX) deficiency (OMIM 220111). Study design In a crossover randomized double-blind clinical trial, 5 children with SLSJ-COX deficiency, who were stable and old enough to comply with VO 2 measurement, were treated with placebo or DMG for 3 days, and with the alternate treatment after a 2-week washout period. VO 2 was measured by indirect calorimetry before and after treatment. Dietary caloric intake was calculated for 3 days before each measurement. Mean caloric intakes per day were 1562 and 1342 kcal.m - 2 before and during placebo, 1336 and 1380 before and during DMG, respectively. Results DMG was well tolerated and, in all cases, resulted in markedly increased blood DMG levels (617 + 203 mmol.L - 1 ), versus 0 to 2 mmol.L - 1 without treatment. Mean VO 2 was lower after administration of either DMG (-1 +/- 3 mL.min - 1 .m - 2 ) or placebo (-6 +/- 4), but neither difference was statistically significant. There was no detectable effect of DMG treatment on blood levels of lactate, pyruvate, bicarbonate, or pH. VO 2 values of patients (range, 101-135 mL.min - 1 .m - 2 ) were lower than published norms (150-160 mL.min - 1 .m - 2 ). Conclusion This study suggests that treatment with DMG does not substantially change VO 2 in children with SLSJ-COX deficiency. (J Pediatr 2003;142:62-6)