Axonal Injury and Myelin Loss in Glutaric Acidemia Type I (ga-1) Mouse Model of Diet Induced Encephalopathy

INTRODUCTION: Glutaric Acidemia type I (GA-1) is an inborn error of lysine, hydroxylysine and tryptophan catabolism. Due to deficiency in glutarylCoA dehydrogenase (Gcdh), these amino acids can not be completely catabolized and lead to accumulation of glutaric acid in the brain, blood and urine. The world wide prevalence is approximately 1:30,000. The common findings at autopsy are severe neuronal loss in the caudate and putamen with spongiform white matter changes [1]. Treatment includes lysine restricted diet during the first few years of life, while it is not clear if individuals with GA1 would benefit from life-long lysine dietary restrictions. In recent years, an increasing number of patients with late onset GA-1 are being recognized. Predominant MRI findings are very similar to leukoencephalopathy, with hyperintense signal restricted to supratentorial white matter on T2-weighted images [2,3]. We hypothesized that constant production of glutaric acid within the brain will lead to neurotoxicity, axonal injury and impaired myelin maintenance. To test this hypothesis we used Gcdh-/mice exposed to lysine enriched diet for 10 months.