1. Influence of early identification and therapy on long-term outcomes in early-onset MTHFR deficiency
- Author
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Yverneau, Mathilde, Leroux, Stéphanie, Imbard, Apolline, Gleich, Florian, Arion, Alina, Moreau, Caroline, Nassogne, Marie-Cécile, Szymanowski, Marie, Tardieu, Marine, Touati, Guy, Bueno, María, Chapman, Kimberly A, Chien, Yin-Hsiu, Huemer, Martina, Ješina, Pavel, Janssen, Mirian C H, Kölker, Stefan, Kožich, Viktor, Lavigne, Christian, Lund, Allan Meldgaard, Mochel, Fanny, Morris, Andrew, Pons, Mónica Ruiz, Porras-Hurtado, Gloria Liliana, Benoist, Jean-François, Damaj, Léna, Schiff, Manuel, E-HOD Consortium, CHU Pontchaillou [Rennes], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Heidelberg University Hospital [Heidelberg], Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Université Catholique de Louvain = Catholic University of Louvain (UCL), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hospital Universitario Virgen del Rocío [Sevilla], Children’s National Health System [Washington, DC, USA], National Taiwan University [Taiwan] (NTU), University Children’s Hospital Zurich, Charles University [Prague] (CU), Radboud University Medical Center [Nijmegen], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Copenhagen University Hospital, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Manchester University NHS Foundation Trust (MFT), Hospital Universitario N.S. de Candelaria [Santa Cruz de Tenerife, Spain], Hôpital Robert Debré Paris, Hôpital Robert Debré, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), European Union [739543], EU-project phase [2012 12 02], SOBI, Recordati Rare Disease Foundation, Aeglea, and Jonchère, Laurent
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newborn screening ,[SDV]Life Sciences [q-bio] ,MTHFR deficiency ,Infant, Newborn ,neurodevelopmental outcome ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,digestive system diseases ,[SDV] Life Sciences [q-bio] ,Cohort Studies ,homocystinuria ,Psychotic Disorders ,EHOD ,Muscle Spasticity ,Genetics ,Humans ,remethylation defects ,Homocystinuria ,Homocysteine ,Genetics (clinical) ,Methylenetetrahydrofolate Reductase (NADPH2) ,Retrospective Studies - Abstract
Contains fulltext : 286882.pdf (Publisher’s version ) (Closed access) MTHFR deficiency is a severe inborn error of metabolism leading to impairment of the remethylation of homocysteine to methionine. Neonatal and early-onset patients mostly exhibit a life-threatening acute neurologic deterioration. Furthermore, data on early-onset patients' long-term outcomes are scarce. The aims of this study were (1) to study and describe the clinical and laboratory parameters of early-onset MTHFR-deficient patients (i.e., ≤3 months of age) and (2) to identify predictive factors for severe neurodevelopmental outcomes in a cohort with early and late onset MTHFR-deficient patients. To this end, we conducted a retrospective, multicentric, international cohort study on 72 patients with MTHFR deficiency from 32 international metabolic centres. Characteristics of the 32 patients with early-onset MTHFR deficiency were described at time of diagnosis and at the last follow-up visit. Logistic regression analysis was used to identify predictive factors of severe neurodevelopmental outcome in a broader set of patients with early and non-early-onset MTHFR deficiency. The majority of early-onset MTHFR-deficient patients (n = 32) exhibited neurologic symptoms (76%) and feeding difficulties (70%) at time of diagnosis. At the last follow-up visit (median follow-up time of 8.1 years), 76% of treated early-onset patients (n = 29) exhibited a severe neurodevelopmental outcome. Among the whole study population of 64 patients, pre-symptomatic diagnosis was independently associated with a significantly better neurodevelopmental outcome (adjusted OR 0.004, [0.002-0.232]; p = 0.003). This study provides evidence for benefits of pre-symptomatic diagnosis and appropriate therapeutic management, highlighting the need for systematic newborn screening for MTHFR deficiency and pre-symptomatic treatment that may improve outcome.
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- 2022
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