Mitochondrial acetoacetyl-CoA thiolase deficiency: basal ganglia impairment may occur independently of ketoacidosis
| العنوان: | Mitochondrial acetoacetyl-CoA thiolase deficiency: basal ganglia impairment may occur independently of ketoacidosis |
|---|---|
| المؤلفون: | Jean-François Benoist, Guy Touati, Nathalie Guffon, Isabelle Rouvet, Dries Dobbelaere, Cécile Acquaviva-Bourdain, Manuel Schiff, François Labarthe, Christine Vianey-Saban, Samia Pichard, Stéphanie Paquay, Pascale de Lonlay, Karine Mention, Monique Elmaleh-Bergès, Hélène Ogier de Baulny, Agnès Bourillon, Vassili Valayannopoulos, Alain Fouilhoux |
| المساهمون: | UCL - (SLuc) Service de neurologie pédiatrique, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL) |
| المصدر: | Journal of Inherited Metabolic Disease, Vol. 40, no.3, p. 415-422 (2017) Journal of Inherited Metabolic Disease Journal of Inherited Metabolic Disease, Springer Verlag, 2017, 40 (3), pp.415-422. ⟨10.1007/s10545-017-0021-y⟩ |
| بيانات النشر: | Springer Netherlands, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Pediatrics, INBORN-ERRORS, [SDV]Life Sciences [q-bio], Ketone Bodies, Basal Ganglia, 0302 clinical medicine, Extrapyramidal symptoms, Basal ganglia, Young adult, BRAIN, Acetyl-CoA C-Acetyltransferase, Child, Genetics (clinical), 2-METHYLACETOACETATE, Putamen, DEFECTS, Acetyl-CoA C-Acyltransferase, 3. Good health, Mitochondria, Globus pallidus, Child, Preschool, Female, medicine.symptom, PROPIONIC ACIDEMIA, Adult, medicine.medical_specialty, 3-OXOTHIOLASE DEFICIENCY, Adolescent, 03 medical and health sciences, Young Adult, Neonatal Screening, Internal medicine, Genetics, medicine, Humans, Decompensation, Isoleucine, Amino Acid Metabolism, Inborn Errors, Retrospective Studies, AMINO-ACID-METABOLISM, Newborn screening, business.industry, ISOLEUCINE DEGRADATION, Infant, Newborn, Infant, Ketosis, medicine.disease, COENZYME-A, Ketoacidosis, 030104 developmental biology, Endocrinology, BETA-KETOTHIOLASE DEFICIENCY, business, 030217 neurology & neurosurgery |
| الوصف: | International audience; Background Mitochondrial acetoacetyl-CoA thiolase (T2) deficiency affects ketone body and isoleucine catabolism. Neurological impairment may occur secondary to ketoacidotic episodes. However, we observed neuromotor abnormalities without ketoacidotic events in two T2-deficient families. We hypothesized that the neurological signs were related to the genetic defect and may occur independently of ketoacidotic episodes. We therefore conducted a retrospective review on a French T2-deficient patient series searching for neuromotor impairment. Methods In total, 26 cases were retrospectively analysed for clinical, biological and neuroimaging data. Results Neurological findings were observed for 6/26 (23%) patients. Among these, two had never experienced ketoacidotic episodes, though they developed extrapyramidal signs with putamen involvement. Two of the other four patients developed neurological abnormalities before the first ketoacidotic crisis, with putamen involvement in one case. The third patient developed extrapyramidal symptoms more than 10 years after the initial decompensation with globus pallidus involvement. The last patient developed extrapyramidal signs immediately after a severe ketoacidotic crisis with putaminal lesions. Conclusions Most T2-deficient patients achieved normal neurodevelopment. However, on account of the role of T2 in isoleucine catabolism, these patients are potentially exposed to accumulation of toxic isoleucine-derived metabolites, which may contribute to neurological impairment. Our findings confirm previous observations that neurological symptoms in T2 deficiency may occur unrelated to ketoacidosis. The role of protein restriction as a preventive measure against neurological symptoms could not be established in this study and deserves further evaluation. Long-term follow-up data on children diagnosed by newborn screening may clarify the pathogenesis of this neurometabolic association. |
| اللغة: | English |
| تدمد: | 0141-8955 1573-2665 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3e95690a6e31fc2412ae31343f873d7Test https://hdl.handle.net/2078.1/194947Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f3e95690a6e31fc2412ae31343f873d7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 01418955 15732665 |
|---|