Pyruvate dehydrogenase deficiency presenting as intermittent isolated acute ataxia.

[pyruvate dehydrogenase deficiency]

The aim of this study is to report and emphasize unusual presentations of pyruvate dehydrogenase (PDH ) deficiency (OMIM 312170 ).PDH activity and PDHA 1 gene were studied in two siblings presenting with intermittent ataxia in childhood . Similar presentations in reported PDH -deficient patients were searched for using the Medline database .Both patients had PDH deficiency caused by a new mutation (G 585 C ) in the PDHA 1 gene , which is predicted to replace a highly conserved glycine at codon 195 by alanine . Although this mutation lies within the thiamine pyrophosphate binding domain , there was no thiamine responsiveness IN VIVO . The patients presented recurrent episodes of acute isolated ataxia in infancy . Both had normal blood and CSF lactate levels . Although symptoms initially resolved between episodes during the first decade , both patients subsequently worsened and developed progressive and severe encephalopathy , leading to death in their twenties . The spectrum of intermittent presentations in PDH deficiency includes episodic ataxia , intermittent peripheral weakness , recurrent dystonia and extrapyramidal movement disorders .PDH deficiency should be considered in patients with unexplained intermittent and recurrent acute neurological symptoms . Long -term prognosis and outcome remain uncertain . PDH deficiency can occur even with normal CSF lactate concentration .