1. Narrative review of glycogen storage disorder type <scp>III</scp> with a focus on neuromuscular, cardiac and therapeutic aspects
- Author
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Philippe Labrune, Giuseppe Ronzitti, Édouard Berling, Karim Wahbi, Alan O’Brien, Francois Michael Petit, Pascal Laforêt, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [AP-HP], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), AP-HP - Hôpital Antoine Béclère [Clamart], Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR‐17‐CE18‐0014, Giuseppe Ronzitti has been supported by Genethon, the 'Association Française contre la Myopathie,' the 'Association Francophone des Glycogénoses,' and the National Research Agency (ANR‐17‐CE18‐0014). All the other authors received no funding for this work., ANR-17-CE18-0014,TRACeGSDIII,Optimisation translationnelle d'un vecteur AAV pour le traitement de GSDIII(2017), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
- Subjects
Adult ,[SDV]Life Sciences [q-bio] ,Cardiomyopathy ,Exercise intolerance ,Hypoglycemia ,Bioinformatics ,Glycogen debranching enzyme activity ,Glycogen Storage Disease Type III ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Muscular Diseases ,glycogen storage disorder ,Genetics ,medicine ,Animals ,Humans ,Child ,Muscle, Skeletal ,Myopathy ,Genetics (clinical) ,030304 developmental biology ,0303 health sciences ,Glycogen ,business.industry ,Genetic Therapy ,metabolic disease ,medicine.disease ,gene therapy ,3. Good health ,Review article ,Disease Models, Animal ,hypoglycemia ,Liver ,chemistry ,Failure to thrive ,medicine.symptom ,business ,cardiomyopathy ,030217 neurology & neurosurgery ,Hepatomegaly ,myopathy - Abstract
International audience; Glycogen storage disorder type III (GSDIII) is a rare inborn error of metabolism due to loss of glycogen debranching enzyme activity, causing inability to fully mobilize glycogen stores and its consequent accumulation in various tissues, notably liver, cardiac and skeletal muscle. In the pediatric population, it classically presents as hepatomegaly with or without ketotic hypoglycemia and failure to thrive. In the adult population, it should also be considered in the differential diagnosis of left ventricular hypertrophy or hypertrophic cardiomyopathy, myopathy, exercise intolerance, as well as liver cirrhosis or fibrosis with subsequent liver failure. In this review article, we first present an overview of the biochemical and clinical aspects of GSDIII. We then focus on the recent findings regarding cardiac and neuromuscular impairment associated with the disease. We review new insights into the pathophysiology and clinical picture of this disorder, including symptomatology, imaging and electrophysiology. Finally, we discuss current and upcoming treatment strategies such as gene therapy aimed at the replacement of the malfunctioning enzyme to provide a stable and long-term therapeutic option for this debilitating disease.
- Published
- 2021