Glut1 Deficiency Syndrome (Glut1DS): State of the art in 2020 and recommendations of the international Glut1DS study group

Epilepsia Open - Tập 5 Số 3 - Trang 354-365 - 2020
Joerg Klepper1, Cigdem I. Akman2, Marisa Armeno3, Stéphane Auvin4, Mackenzie C. Cervenka5, J. Helen Cross6, Valentina De Giorgis7, Adela Della Marina8, Kristin Engelstad2, Nicole Heußinger9, Eric H. Kossoff10, Wilhelmina G. Leen11, B. Leiendecker8, Umrao R. Monani12, Hirokazu Oguni13, Elizabeth Neal14, Juan M. Pascual15, Toni S. Pearson16, Roser Pons17, Ingrid E. Scheffer18, Pierangelo Veggiotti19, Michèl A.A.P. Willemsen20, Sameer M. Zuberi21, Darryl C. De Vivo2
1Children’s Hospital Aschaffenburg-Alzenau, Aschaffenburg, Germany
2Department of Neurology and Pediatrics, Vagelos College of Physicians and Surgeons at Columbia University, New York, NY, USA
3Department of Nutrition, Hospital Pediatria JP Garrahan, Buenos Aires, Argentina
4Department of Pediatric Neurology CHU Hôpital Robert Debre APHP Paris France
5Department of Neurology, Comprehensive Epilepsy Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
6UCL NIHR BRC Great Ormond Street Institute of Child Health, London, UK
7Department of Child Neurology and Psychiatry, IRCCS Mondino Foundation, Pavia, Italy
8Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, Centre for Neuromuscular Disorders in Children, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
9Department of Pediatric Neurology, Paracelsus Medical Private University, Nuremberg, Germany
10Departments of Neurology and Pediatrics, Johns Hopkins University, Baltimore, MD, USA
11Department of Neurology, Canisius Wilhemina Hospital, Nijmegen, The Netherlands
12Center for Motor Neuron Biology & Disease Departments of Neurology and Pathology & Cell Biology Columbia University Irving Medical Center New York NY USA
13Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan
14Matthew's Friends Charity & Clinics Lingfield UK
15Departments of Neurology and Neurotherapeutics, Physiology and Pediatrics, Eugene McDermott Center for Human Growth and Development, The University of Texas Southwestern Medical Center, Dallas, TX, USA
16Mount Sinai Center for Headache & Pain Medicine New York NY USA
17First Department of Pediatrics, Agia Sofia Hospital, University of Athens, Athens, Greece
18Florey and Murdoch Institutes, Austin Health and Royal Children's Hospital, The University of Melbourne, Melbourne, Victoria, Australia
19Pediatric Neurology V. Buzzi Hospital, Child Neuropsychiatry University of Milan, Milan, Italy
20Department of Pediatric Neurology, Radboud University Medical Centre, Amalia Children's Hospital, Nijmegen, Netherlands
21Royal Hospital for Children & College of Medical Veterinary & Life Sciences University of Glasgow Glasgow UK

Tóm tắt

AbstractGlut1 deficiency syndrome (Glut1DS) is a brain energy failure syndrome caused by impaired glucose transport across brain tissue barriers. Glucose diffusion across tissue barriers is facilitated by a family of proteins including glucose transporter type 1 (Glut1). Patients are treated effectively with ketogenic diet therapies (KDT) that provide a supplemental fuel, namely ketone bodies, for brain energy metabolism. The increasing complexity of Glut1DS, since its original description in 1991, now demands an international consensus statement regarding diagnosis and treatment. International experts (n = 23) developed a consensus statement utilizing their collective professional experience, responses to a standardized questionnaire, and serial discussions of wide‐ranging issues related to Glut1DS. Key clinical features signaling the onset of Glut1DS are eye‐head movement abnormalities, seizures, neurodevelopmental impairment, deceleration of head growth, and movement disorders. Diagnosis is confirmed by the presence of these clinical signs, hypoglycorrhachia documented by lumbar puncture, and genetic analysis showing pathogenic SLC2A1 variants. KDT represent standard choices with Glut1DS‐specific recommendations regarding duration, composition, and management. Ongoing research has identified future interventions to restore Glut1 protein content and function. Clinical manifestations are influenced by patient age, genetic complexity, and novel therapeutic interventions. All clinical phenotypes will benefit from a better understanding of Glut1DS natural history throughout the life cycle and from improved guidelines facilitating early diagnosis and prompt treatment. Often, the presenting seizures are treated initially with antiseizure drugs before the cause of the epilepsy is ascertained and appropriate KDT are initiated. Initial drug treatment fails to treat the underlying metabolic disturbance during early brain development, contributing to the long‐term disease burden. Impaired development of the brain microvasculature is one such complication of delayed Glut1DS treatment in the postnatal period. This international consensus statement should facilitate prompt diagnosis and guide best standard of care for Glut1DS throughout the life cycle.

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