Basal ganglia involvement in mitochondrial acetoacetyl-CoA thiolase deficiency
(2015) European Metabolic Group Conference — Location: Venice (11.June.2015)
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- (en) Background & Objectives: Mitochondrial acetoacetyl-CoA thiolase (T2) deficiency affects both ketone bodies and isoleucine catabolism. Neurological impairment can occur as a result from ketoacidotic episodes. However, it has been observed without ketoacidotic events in two T2-deficient families from our hospital. We reviewed the French cohort to document this neurological involvement. Methods: Twenty six cases were retrospectively analyzed. Clinical, biological and radiological data were collected. Results: Neurological signs were observed in 6/26 patients: 2 had never experienced ketoacidotic episodes and developed extrapyramidal signs with putamen involvement, 2 developed neurological abnormalities before the first ketoacidotic crisis and putamen was involved in one case, 1 developed extryramidal symptoms more than 10 years after the initial decompensation with involvement of pallidi and 1 experienced extrapyramidal signs with lesions in putamen immediately after a severe ketoacidotic episode. Conclusion: Due to the key role of T2 in isoleucine catabolism, T2-deficient patients are exposed to accumulation of toxic isoleucine-derived acyl-CoA esters in brain mitochondria suggesting that T2 deficiency should be reconsidered in clinical practice not only as a ketolysis defect but also as an organic aciduria giving rise to progressive and chronic intoxication. The impact of protein restriction as a preventive effect on neurological symptoms remains to be studied.
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Paquay, S., de Lonlay, P., Dobbelaere, D., Fouilhoux, A., Guffon, N., Labarthe, F., Mention, K., Touati, G., Valayannopoulos, V., Vianey-Saban, C., Schiff, M., & et al. (2015). Basal ganglia involvement in mitochondrial acetoacetyl-CoA thiolase deficiency. European Metabolic Group Conference, Venice. https://hdl.handle.net/2078.5/218752