Frontiers in Genetics (Feb 2024)
Brain function in classic galactosemia, a galactosemia network (GalNet) members review
- Bianca Panis,
- Bianca Panis,
- Bianca Panis,
- E. Naomi Vos,
- E. Naomi Vos,
- E. Naomi Vos,
- E. Naomi Vos,
- E. Naomi Vos,
- Ivo Barić,
- Annet M. Bosch,
- Annet M. Bosch,
- Annet M. Bosch,
- Martijn C. G. J. Brouwers,
- Martijn C. G. J. Brouwers,
- Alberto Burlina,
- Alberto Burlina,
- David Cassiman,
- David J. Coman,
- María L. Couce,
- María L. Couce,
- Anibh M. Das,
- Anibh M. Das,
- Didem Demirbas,
- Aurélie Empain,
- Aurélie Empain,
- Matthias Gautschi,
- Olga Grafakou,
- Olga Grafakou,
- Stephanie Grunewald,
- Sandra D. K. Kingma,
- Sandra D. K. Kingma,
- Ina Knerr,
- Elisa Leão-Teles,
- Elisa Leão-Teles,
- Dorothea Möslinger,
- Dorothea Möslinger,
- Elaine Murphy,
- Katrin Õunap,
- Katrin Õunap,
- Adriana Pané,
- Adriana Pané,
- Sabrina Paci,
- Sabrina Paci,
- Rossella Parini,
- Rossella Parini,
- Isabel A. Rivera,
- Sabine Scholl-Bürgi,
- Ida V. D. Schwartz,
- Triantafyllia Sdogou,
- Triantafyllia Sdogou,
- Loai A. Shakerdi,
- Anastasia Skouma,
- Anastasia Skouma,
- Karolina M. Stepien,
- Eileen P. Treacy,
- Susan Waisbren,
- Gerard T. Berry,
- M. Estela Rubio-Gozalbo,
- M. Estela Rubio-Gozalbo,
- M. Estela Rubio-Gozalbo,
- M. Estela Rubio-Gozalbo,
- M. Estela Rubio-Gozalbo
Affiliations
- Bianca Panis
- Department of Pediatrics, MosaKids Children’s Hospital, Maastricht University Medical Centre, Maastricht, Netherlands
- Bianca Panis
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Bianca Panis
- United for Metabolic Diseases (UMD), Amsterdam, Netherlands
- E. Naomi Vos
- Department of Pediatrics, MosaKids Children’s Hospital, Maastricht University Medical Centre, Maastricht, Netherlands
- E. Naomi Vos
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- E. Naomi Vos
- United for Metabolic Diseases (UMD), Amsterdam, Netherlands
- E. Naomi Vos
- Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, Netherlands
- E. Naomi Vos
- GROW School for Oncology and Reproduction, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
- Ivo Barić
- Department of Pediatrics, University Hospital Center Zagreb, Croatia, and School of Medicine, University of Zagreb, Zagreb, Croatia
- Annet M. Bosch
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Annet M. Bosch
- United for Metabolic Diseases (UMD), Amsterdam, Netherlands
- Annet M. Bosch
- Department of Pediatrics, Division of Metabolic Diseases, Emma Children’s Hospital, Amsterdam University Medical Center, Amsterdam Gastroenterology Endocrinology Metabolism, Inborn Errors of Metabolism, Amsterdam, Netherlands
- Martijn C. G. J. Brouwers
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Martijn C. G. J. Brouwers
- Department of Internal Medicine, Division of Endocrinology and Metabolic Disease, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, Netherlands
- Alberto Burlina
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Alberto Burlina
- Division of Inherited Metabolic Diseases, Reference Centre Expanded Newborn Screening, University Hospital Padova, Padova, Italy
- David Cassiman
- 0Laboratory of Hepatology, Department of Chronic Diseases, Metabolism and Ageing, Faculty of Medicine, KU Leuven, Leuven, Belgium
- David J. Coman
- 1Queensland Children’s Hospital, Children’s Health Queensland, Brisbane, QLD, Australia
- María L. Couce
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- María L. Couce
- 2Department of Pediatrics, Diagnosis and Treatment Unit of Congenital Metabolic Diseases, University Clinical Hospital of Santiago de Compostela, IDIS-Health Research Institute of Santiago de Compostela, CIBERER, RICORS Instituto Salud Carlos III, Santiago de Compostela, Spain
- Anibh M. Das
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Anibh M. Das
- 3Department of Paediatrics, Pediatric Metabolic Medicine, Hannover Medical School, Hannover, Germany
- Didem Demirbas
- 4Division of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, Manton Center for Orphan Disease Research, Boston, MA, United States
- Aurélie Empain
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Aurélie Empain
- 5Department of Paediatrics, Metabolic and Nutrition Unit, Division of Endocrinology, Diabetes and Metabolism, University Hospital for Children Queen Fabiola, Bruxelles, Belgium
- Matthias Gautschi
- 6Department of Paediatrics, Institute of Clinical Chemistry, Inselspital, Bern University Hospital, Swiss Reference Centre for Inborn Errors of Metabolism, Site Bern, Division of Pediatric Endocrinology, Diabetes and Metabolism, University of Bern, Bern, Switzerland
- Olga Grafakou
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Olga Grafakou
- 7IEM Clinic, Arch Makarios III Hospital, Nicosia, Cyprus
- Stephanie Grunewald
- 8Metabolic Unit Great Ormond Street Hospital and Institute for Child Health, University College London, London, United Kingdom
- Sandra D. K. Kingma
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Sandra D. K. Kingma
- 9Centre for Metabolic Diseases, University Hospital Antwerp, University of Antwerp, Antwerp, Belgium
- Ina Knerr
- 0National Centre for Inherited Metabolic Disorders, Children’s Health Ireland at Temple Street, University College Dublin, Dublin, Ireland
- Elisa Leão-Teles
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Elisa Leão-Teles
- 1Reference Centre of Inherited Metabolic Diseases, Centro Hospitalar Universitário São João, Porto, Portugal
- Dorothea Möslinger
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Dorothea Möslinger
- 2Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
- Elaine Murphy
- 3Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery (NHNN), London, United Kingdom
- Katrin Õunap
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Katrin Õunap
- 4Genetics and Personalized Medicine Clinic, Faculty of Medicine, Tartu University Hospital, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
- Adriana Pané
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Adriana Pané
- 5Endocrinology and Nutrition Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Sabrina Paci
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Sabrina Paci
- 6Inborn Errors of Metabolism, Clinical Department of Pediatrics, San Paolo Hospital - ASST Santi Paolo e Carlo, University of Milan, Milan, Italy
- Rossella Parini
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Rossella Parini
- 7Rare Diseases Unit, Department of Internal Medicine, San Gerardo Hospital IRCCS, Monza, Italy
- Isabel A. Rivera
- 8iMed.ULisboa–Instituto de Investigação do Medicamento, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal
- Sabine Scholl-Bürgi
- 9Department of Child and Adolescent Health, Division of Pediatrics I-Inherited Metabolic Disorders, Medical University Innsbruck, Innsbruck, Austria
- Ida V. D. Schwartz
- 0Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil
- Triantafyllia Sdogou
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Triantafyllia Sdogou
- 1Newborn Screening Department, Institute of Child Health, Athens, Greece
- Loai A. Shakerdi
- 2Adult Metabolics/Genetics, National Centre for Inherited Metabolic Disorders, The Mater Misericordiae University Hospital, Dublin, Ireland
- Anastasia Skouma
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- Anastasia Skouma
- 1Newborn Screening Department, Institute of Child Health, Athens, Greece
- Karolina M. Stepien
- 3Salford Royal Organisation, Northern Care Alliance NHS Foundation Trust, Salford, United Kingdom
- Eileen P. Treacy
- 4School of Medicine, Trinity College Dublin, National Rare Diseases Office, Mater Misericordiae University Hospital, Dublin, Ireland
- Susan Waisbren
- 4Division of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, Manton Center for Orphan Disease Research, Boston, MA, United States
- Gerard T. Berry
- 4Division of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, Manton Center for Orphan Disease Research, Boston, MA, United States
- M. Estela Rubio-Gozalbo
- Department of Pediatrics, MosaKids Children’s Hospital, Maastricht University Medical Centre, Maastricht, Netherlands
- M. Estela Rubio-Gozalbo
- European Reference Network for Hereditary Metabolic Disorders (MetabERN) Member, Padova, Italy
- M. Estela Rubio-Gozalbo
- United for Metabolic Diseases (UMD), Amsterdam, Netherlands
- M. Estela Rubio-Gozalbo
- Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, Netherlands
- M. Estela Rubio-Gozalbo
- GROW School for Oncology and Reproduction, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
- DOI
- https://doi.org/10.3389/fgene.2024.1355962
- Journal volume & issue
-
Vol. 15
Abstract
Classic galactosemia (CG, OMIM #230400, ORPHA: 79,239) is a hereditary disorder of galactose metabolism that, despite treatment with galactose restriction, affects brain function in 85% of the patients. Problems with cognitive function, neuropsychological/social emotional difficulties, neurological symptoms, and abnormalities in neuroimaging and electrophysiological assessments are frequently reported in this group of patients, with an enormous individual variability. In this review, we describe the role of impaired galactose metabolism on brain dysfunction based on state of the art knowledge. Several proposed disease mechanisms are discussed, as well as the time of damage and potential treatment options. Furthermore, we combine data from longitudinal, cross-sectional and retrospective studies with the observations of specialist teams treating this disease to depict the brain disease course over time. Based on current data and insights, the majority of patients do not exhibit cognitive decline. A subset of patients, often with early onset cerebral and cerebellar volume loss, can nevertheless experience neurological worsening. While a large number of patients with CG suffer from anxiety and depression, the increased complaints about memory loss, anxiety and depression at an older age are likely multifactorial in origin.
Keywords
