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Dietary energy intakes and fecal fat losses did not differ between the groups. Metabolic rates while sleeping and quietly awake were 23% lower (P &lt; .05) in Rett syndrome girls than in controls; metabolic rates while actively awake did not differ between the groups. However, because of the 2.4-fold greater time (P &lt; .001) spent in involuntary motor movement, energy expenditure associated with activity was twofold greater (P &lt; .05) in Rett syndrome girls than in controls. Although total daily energy expenditure of the two groups did not differ significantly, energy balance was less positive in the Rett syndrome girls than in the controls. This small difference in energy balance, if sustained over months to years, is sufficient to account for growth failure in Rett syndrome girls. 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