Abstract
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 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.
Key words
Rett syndrome - Oxidative metabolism - Lactic acid - Fasting - Glucose load - Alanine load
