Oxidative metabolism in Rett syndrome: 1. Clinical studies

The etiology of Rett syndrome (RS) remains a mystery. The clinical phenotype has similarities to that of patients with mitochondrial defects of oxidative metabolism. There is evidence of lactate and pyruvate elevations in blood and CSF in some patients. Over the last 10 years we have studied girls with RS looking for evidence of a defect in oxidative metabolism. We present data on lactate and pyruvate blood measurements in 30 patients with RS with repeated measurements performed over time in many. Taken as a whole the means of measurements of lactate and pyruvate fall within the control range, however, individual patients have marked elevation of both lactate and pyruvate with considerable fluctuation over time. Nine girls with typical RS were studied in detail using a clinical protocol designed to identify disorders of oxidative metabolism. These patients underwent fasting for 24 hours, glucose loading and alanine loading tests. Seven girls had skin and muscle biopsies performed. One patient admitted with particularly high blood lactate levels underwent hourly blood collections over a 24 hour period during which state of alertness was noted and respiratory monitoring was performed. In this patient serial blood sampling for lactate performed. In this patient serial blood sampling for lactate performed with oxypneumocardiogram recording demonstrated a fall in plasma lactate to normal levels during sleep when the respiratory pattern was normal. Such fluctuations of plasma lactate apparently correlated with sleep/wake state and respiration suggest that in some patients with RS lactate elevations may arise from respiratory abnormalities. Other positive findings included prediabetic glucose responses in three girls. Ammonia levels following alanine loading were normal in all patients.