The Rett syndrome and CSF lactic acid patterns.

We investigated both blood and cerebrospinal fluid (CSF) lactate and pyruvate levels in seven girls with the Rett syndrome (RS) and evaluated the relationship between CSF lactate and pyruvate levels and the clinical manifestations, particularly seizures, anticonvulsant medication, and breathing dysfunction including breath holding, apnea and hyperventilation. Elevated lactate and pyruvate levels in CSF with normal serum lactate were found in two RS patients. Elevated CSF lactate correlated significantly with the clinical occurrence of hyperventilation (P0 = 0.048, Fisher exact probability). We measured native and dichloroacetate (DCA)-activated pyruvate dehydrogenase (PDH) complex activities in two patients (#1 and 2) using cultured lymphoblastoid cell lines which were transformed by EB virus and the results were normal. We also analyzed CSF citric acid intermediates from 7 RS patients including citric acid, cis-aconitate, alpha-ketoglutarate, succinate, fumarate, malate and oxaloacetate. These concentrations were not significantly different from those control patients (N = 21). An elevated lactate level may be a clue to clarify the etiology of RS.