December 06, 2022; 99 (23) Research Article
Association Between Lysine Reduction Therapies and Cognitive Outcomes in Patients With Pyridoxine-Dependent Epilepsy
Curtis R. Coughlin, Laura A. Tseng, Levinus A. Bok, Hans Hartmann, Emma Footitt, View ORCID ProfilePasquale Striano, Brahim M. Tabarki, Roelineke J. Lunsing, Sylvia Stockler-Ipsiroglu, Shanlea Gordon, Johan L.K. Van Hove, Jose E. Abdenur, Monica Boyer, Nicola Longo, Ashley Andrews, Mirian C.H. Janssen, View ORCID ProfileAnnemiek van Wegberg, Chitra Prasad, View ORCID ProfileAsuri N. Prasad, View ORCID ProfileMolly M. Lamb, Frits A. Wijburg, Sidney M. Gospe, Clara van Karnebeek, on behalf of the International PDE Consortium
First published August 25, 2022, DOI: https://doi.org/10.1212/WNL.0000000000201222
Curtis R. Coughlin
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
II, PhD, MS, MBELaura A. Tseng
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MDLevinus A. Bok
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MD, PhDHans Hartmann
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MDEmma Footitt
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MBBS, PhDPasquale Striano
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MD, PhDBrahim M. Tabarki
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MDRoelineke J. Lunsing
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MD, PhDSylvia Stockler-Ipsiroglu
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MD, PhDShanlea Gordon
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MAJohan L.K. Van Hove
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MD, PhDJose E. Abdenur
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MDMonica Boyer
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
CPNPNicola Longo
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MD, PhDAshley Andrews
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MD, PhDMirian C.H. Janssen
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MD, PhDAnnemiek van Wegberg
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
PhDChitra Prasad
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MDAsuri N. Prasad
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MBBS, MDMolly M. Lamb
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
PhDFrits A. Wijburg
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MD, PhDSidney M. Gospe Jr
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MD, PhDClara van Karnebeek
From the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
MD, PhDFrom the Section of Clinical Genetics and Metabolism (C.R.C., J.L.K.V.H.), Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora; Department of Pediatrics (L.A.T., F.A.W., C.v.K.), Emma Children's Hospital and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam; United for Metabolic Diseases (L.A.T., C.v.K.); Department of Pediatrics and Neonatology (L.A.B.), Máxima Medical Center, Veldhoven, the Netherlands; Clinic for Pediatric Kidney (H.H.), Liver, and Metabolic Diseases, Hannover Medical School, Germany; Department of Metabolic Paediatrics (E.F.), Great Ormond Street Hospital, London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (P.S.), IRCCS “G. Gaslini” Institute, Genova; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (P.S.), University of Genova, Italy; Prince Sultan Military Medical City (B.M.T.), Riyadh, Saudi Arabia; Department of Paediatric Neurology (R.J.L.), University Medical Center Groningen, University of Groningen, the Netherlands; Division of Biochemical Genetics (S.S.-I.), BC Children's Hospital, University of British Columbia; BC Children's Hospital Research Institute (S.G.), Vancouver, British Columbia, Canada; Division of Metabolic Disorders (J.E.A., M.B.), CHOC Children's Hospital, Orange, CA; Division of Medical Genetics (N.L., A.A.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Internal Medicine (M.C.H.J.), Radboud University Medical Center, Nijmegen; Department of Gastroenterology and Hepatology (A.v.W.), Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands; Department of Pediatrics (C.P., A.N.P.), Western University, London, Ontario, Canada; Department of Epidemiology and Center for Global Health (M.M.L.), Colorado School of Public Health, Aurora; Departments of Neurology and Pediatrics (S.M.G.), University of Washington, Seattle; Seattle Children's Research Institute (S.M.G.), WA; Department of Pediatrics (S.M.G.), Duke University, Durham, NC; and Department of Human Genetics (C.v.K.), Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
Association Between Lysine Reduction Therapies and Cognitive Outcomes in Patients With Pyridoxine-Dependent Epilepsy
Curtis R. Coughlin, Laura A. Tseng, Levinus A. Bok, Hans Hartmann, Emma Footitt, Pasquale Striano, Brahim M. Tabarki, Roelineke J. Lunsing, Sylvia Stockler-Ipsiroglu, Shanlea Gordon, Johan L.K. Van Hove, Jose E. Abdenur, Monica Boyer, Nicola Longo, Ashley Andrews, Mirian C.H. Janssen, Annemiek van Wegberg, Chitra Prasad, Asuri N. Prasad, Molly M. Lamb, Frits A. Wijburg, Sidney M. Gospe, Clara van Karnebeek, on behalf of the International PDE Consortium
Neurology Dec 2022, 99 (23) e2627-e2636; DOI: 10.1212/WNL.0000000000201222
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Abstract
Background and Objectives Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is a developmental epileptic encephalopathy characterized by seizure improvement after pyridoxine supplementation. Adjunct lysine reduction therapies (LRTs) reduce the accumulation of putative neurotoxic metabolites with the goal to improve developmental outcomes. Our objective was to examine the association between treatment with LRTs and cognitive outcomes.
Methods Participants were recruited from within the International Registry for Patients with Pyridoxine-Dependent Epilepsy from August 2014 through March 2021. The primary outcome was standardized developmental test scores associated with overall cognitive ability. The relationship between test scores and treatment was analyzed with multivariable linear regression using a mixed-effects model. A priori, we hypothesized that treatment in early infancy with pyridoxine and LRTs would result in a normal developmental outcome. A subanalysis was performed to evaluate the association between cognitive outcome and LRTs initiated in the first 6 months of life.
Results A total of 112 test scores from 60 participants were available. On average, treatment with pyridoxine and LRTs was associated with a nonsignificant increase of 6.9 points (95% CI −2.7 to 16.5) on developmental testing compared with treatment with pyridoxine alone. For the subanalysis, a total of 14 developmental testing scores were available from 8 participants. On average, treatment with pyridoxine and LRTs in the first 6 months of life was associated with a significant increase of 21.9 points (95% CI 1.7–42.0) on developmental testing.
Discussion Pyridoxine and LRTs at any age was associated with mild improvement in developmental testing, and treatment in early infancy was associated with a clinically significant increase in developmental test scores. These results provide insight into the mechanism of intellectual and developmental disability in PDE-ALDH7A1 and emphasize the importance of treatment in early infancy with both pyridoxine and LRTs.
Classification of Evidence This study provides Class IV evidence that in PDE-ALDH7A1, pyridoxine and LRTs compared with pyridoxine alone is not significantly associated with overall higher developmental testing scores, but treatment in the first 6 months of life is associated with significantly higher developmental testing scores.
Glossary
- α-AASA=
- α-aminoadipic semialdehyde;
- ID/DD=
- intellectual disability or developmental disability;
- IQR=
- interquartile range;
- LRT=
- lysine reduction therapy;
- PDE=
- pyridoxine-dependent epilepsy
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work as co-first authors.
Coinvestigators are listed at links.lww.com/WNL/C279.
Submitted and externally peer reviewed. The handling editor was Renee Shellhaas, MD, MS.
Editorial, page 1025
Class of Evidence: NPub.org/coe
- Received February 26, 2022.
- Accepted in final form July 26, 2022.
- © 2022 American Academy of Neurology
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