OXIDATIVE-METABOLISM IN RETT-SYNDROME .1. CLINICAL-STUDIES

The etiology of Rett syndrome (RS) remains a mystery. The clinical phe notype has similarities to that of patients with mitochondrial defects of oxidative metabolism. There is evidence of lactate and pyruvate el evations 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 oxidati ve metabolism. We present data on lactate and Pyruvate blood measureme nts in 30 patients with RS with repeated measurements performed over t ime 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 f luctuation over time. Nine girls with typical RS were studied in detai l using a clinical protocol designed to identify disorders of oxidativ e metabolism. These patients underwent fasting for 24 hours, glucose l oading and alanine loading tests. Seven girls had skin and muscle biop sies performed. One patient admitted with particularly high blood lact ate levels underwent hourly blood collections over a 24 hour period du ring which state oi alertness was noted and respiratory monitoring was performed. Ln this patient serial blood sampling for lactate I perfor med with oxypneumocardiogram recording demon strated a fall in plasma lactate to normal levels during sleep when the respiratory pattern was normal. Such fluctuations of plasma lactate apparently correlated wit h 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 girl s. Ammonia levels following alanine loading were normal in all patient s.