Kendra J Bjoraker1, Michael A Swanson1, Curtis R Coughlin1, John Christodoulou2, Ee S Tan2, Mark Fergeson3, Sarah Dyack4, Ayesha Ahmad5, Marisa W Friederich1, Elaine B Spector1, Geralyn Creadon-Swindell1, M Antoinette Hodge6, Sommer Gaughan1, Casey Burns1, Johan L K Van Hove7. 1. Department of Pediatrics, University of Colorado, Aurora, CO. 2. Western Sydney Genetics Program, Children's Hospital at Westmead, and Disciplines of Pediatrics and Child Health and Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. 3. Department of Pediatrics, Oklahoma University, Oklahoma City, OK. 4. Department of Pediatrics, Dalhousie University, IWK Health Centre, Halifax, Nova Scotia, Canada. 5. Division of Pediatric Genetics, University of Michigan, Ann Arbor, MI. 6. Child Development Unit, Children's Hospital at Westmead, Sydney, New South Wales, Australia. 7. Department of Pediatrics, University of Colorado, Aurora, CO. Electronic address: Johan.Vanhove@ucdenver.edu.
Abstract
OBJECTIVE: To evaluate the impact of sodium benzoate and dextromethorphan treatment on patients with the attenuated form of nonketotic hyperglycinemia. STUDY DESIGN: Families were recruited with 2 siblings both affected with attenuated nonketotic hyperglycinemia. Genetic mutations were expressed to identify residual activity. The outcome on developmental progress and seizures was compared between the first child diagnosed and treated late with the second child diagnosed at birth and treated aggressively from the newborn period using dextromethorphan and benzoate at dosing sufficient to normalize plasma glycine levels. Both siblings were evaluated with similar standardized neurodevelopmental measures. RESULTS: In each sibling set, the second sibling treated from the neonatal period achieved earlier and more developmental milestones, and had a higher developmental quotient. In 3 of the 4 sibling pairs, the younger sibling had no seizures whereas the first child had a seizure disorder. The adaptive behavior subdomains of socialization and daily living skills improved more than motor skills and communication. CONCLUSIONS: Early treatment with dextromethorphan and sodium benzoate sufficient to normalize plasma glycine levels is effective at improving outcome if used in children with attenuated disease with mutations providing residual activity and when started from the neonatal period.
OBJECTIVE: To evaluate the impact of sodium benzoate and dextromethorphan treatment on patients with the attenuated form of nonketotic hyperglycinemia. STUDY DESIGN: Families were recruited with 2 siblings both affected with attenuated nonketotic hyperglycinemia. Genetic mutations were expressed to identify residual activity. The outcome on developmental progress and seizures was compared between the first child diagnosed and treated late with the second child diagnosed at birth and treated aggressively from the newborn period using dextromethorphan and benzoate at dosing sufficient to normalize plasma glycine levels. Both siblings were evaluated with similar standardized neurodevelopmental measures. RESULTS: In each sibling set, the second sibling treated from the neonatal period achieved earlier and more developmental milestones, and had a higher developmental quotient. In 3 of the 4 sibling pairs, the younger sibling had no seizures whereas the first child had a seizure disorder. The adaptive behavior subdomains of socialization and daily living skills improved more than motor skills and communication. CONCLUSIONS: Early treatment with dextromethorphan and sodium benzoate sufficient to normalize plasma glycine levels is effective at improving outcome if used in children with attenuated disease with mutations providing residual activity and when started from the neonatal period.
Authors: Raphaëlle Riché; Meijiang Liao; Izabella A Pena; Kit-Yi Leung; Nathalie Lepage; Nicolas DE Greene; Kyriakie Sarafoglou; Lisa A Schimmenti; Pierre Drapeau; Éric Samarut Journal: JCI Insight Date: 2018-11-02
Authors: A Sadhwani; J M Willen; H Miller; R Barbieri-Welge; L T Horowitz; L M Noll; S Peters; R Hundley; L M Bird; W H Tan Journal: J Intellect Disabil Res Date: 2019-12-19
Authors: Curtis R Coughlin; Michael A Swanson; Kathryn Kronquist; Cécile Acquaviva; Tim Hutchin; Pilar Rodríguez-Pombo; Marja-Leena Väisänen; Elaine Spector; Geralyn Creadon-Swindell; Ana M Brás-Goldberg; Elisa Rahikkala; Jukka S Moilanen; Vincent Mahieu; Gert Matthijs; Irene Bravo-Alonso; Celia Pérez-Cerdá; Magdalena Ugarte; Christine Vianey-Saban; Gunter H Scharer; Johan L K Van Hove Journal: Genet Med Date: 2016-06-30 Impact factor: 8.822