1. Autosomal Recessive Cerebellar Ataxias With Elevated Alpha‐Fetoprotein: Uncommon Diseases, Common Biomarker
- Author
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Mathilde Renaud, Christine Tranchant, Michel Koenig, Mathieu Anheim, Service de Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Herrada, Anthony
- Subjects
MESH: Multifunctional Enzymes ,Cerebellar Ataxia ,MESH: DNA Helicases ,MESH: Ataxia Telangiectasia ,Ataxia Telangiectasia ,alpha-fetoprotein ,03 medical and health sciences ,0302 clinical medicine ,Cogan Syndrome ,Humans ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,MESH: Cogan Syndrome ,030304 developmental biology ,0303 health sciences ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,MESH: Humans ,MESH: RNA Helicases ,oculomotor apraxia ,DNA Helicases ,Nuclear Proteins ,Multifunctional Enzymes ,MESH: Phosphotransferases (Alcohol Group Acceptor) ,digestive system diseases ,MESH: Cerebellar Ataxia ,3. Good health ,DNA-Binding Proteins ,Phosphotransferases (Alcohol Group Acceptor) ,DNA Repair Enzymes ,MESH: DNA Repair Enzymes ,recessive ataxia ,Neurology ,DNA/RNA repair ,MESH: Biomarkers ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,alpha-Fetoproteins ,MESH: alpha-Fetoproteins ,Neurology (clinical) ,MESH: Nuclear Proteins ,Biomarkers ,RNA Helicases ,MESH: DNA-Binding Proteins ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,030217 neurology & neurosurgery - Abstract
International audience; alpha-Fetoprotein (AFP) is a biomarker of several autosomal recessive cerebellar ataxias (ARCAs), especially ataxia telangiectasia (AT) and ataxia with oculomotor apraxia (AOA) type 2 (AOA2). More recently, slightly elevated AFP has been reported in AOA1 and AOA4. Interestingly, AOA1, AOA2, AOA4, and AT are overlapping ARCAs characterized by oculomotor apraxia, with oculocephalic dissociation, choreo-dystonia, and/or axonal sensorimotor neuropathy, in addition to cerebellar ataxia with cerebellar atrophy. The genetic backgrounds in these disorders play central roles in nuclear maintenance through DNA repair [ATM (AT), APTX (AOA1), or PNKP (AOA4)] or RNA termination [SETX (AOA2)]. Partially discriminating thresholds of AFP have been proposed as a way to distinguish between ARCAs with elevated AFP. In these entities, elevated AFP may be an epiphenomenon as a result of liver transcriptional dysregulation. AFP is a simple and reliable biomarker for the diagnosis of ARCA in performance and interpretation of next-generation sequencing. Here, we evaluated clinical, laboratory, imaging, and molecular data of the group of ARCAs that share elevated AFP serum levels that have been described in the past two decades. © 2020 International Parkinson and Movement Disorder Society.
- Published
- 2020