In Reply In their letter, Dager et al suggest several ways in which the findings of our study1 could be strengthened.
First, they posit that magnetic resonance imaging (MRI) structural changes would support the interpretation that elevated brain lactate is secondary to mitochondrial dysfunction. However, a review on this topic concluded that “neither normal brain MRI nor normal [magnetic resonance spectroscopy] can exclude the diagnosis of respiratory chain deficiency.”2 It has long been known that MRI structural changes may or may not be present in mitochondrial diseases, and their absence does not exclude the presence of mitochondrial disease. Moreover, in a sample of autistic individuals who were not preselected on the basis of having classic mitochondrial disease, as in the sample we studied, it seems likely that structural brain MRI changes would be even less common. (It is worth noting that we did acquire structural data in this sample but the anatomical findings have yet to be reported.) Finally, the lactate elevations seem to have been uniquely localized in specific brain regions of these participants, suggesting that anatomical abnormalities, even if present, would have been highly localized and different across participants, making their detection difficult.