{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:43:07Z","timestamp":1790962987111,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["2012 12 02"],"award-info":[{"award-number":["2012 12 02"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>MTHFR deficiency is a severe inborn error of metabolism leading to impairment of the remethylation of homocysteine to methionine. Neonatal and early\u2010onset patients mostly exhibit a life\u2010threatening acute neurologic deterioration. Furthermore, data on early\u2010onset patients' long\u2010term outcomes are scarce. The aims of this study were (1) to study and describe the clinical and laboratory parameters of early\u2010onset MTHFR\u2010deficient patients (i.e., \u22643\u00a0months of age) and (2) to identify predictive factors for severe neurodevelopmental outcomes in a cohort with early and late onset MTHFR\u2010deficient 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\u2010onset MTHFR deficiency were described at time of diagnosis and at the last follow\u2010up visit. Logistic regression analysis was used to identify predictive factors of severe neurodevelopmental outcome in a broader set of patients with early and non\u2010early\u2010onset MTHFR deficiency. The majority of early\u2010onset MTHFR\u2010deficient patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a032) exhibited neurologic symptoms (76%) and feeding difficulties (70%) at time of diagnosis. At the last follow\u2010up visit (median follow\u2010up time of 8.1\u2009years), 76% of treated early\u2010onset patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a029) exhibited a severe neurodevelopmental outcome. Among the whole study population of 64 patients, pre\u2010symptomatic diagnosis was independently associated with a significantly better neurodevelopmental outcome (adjusted OR 0.004, [0.002\u20130.232]; <jats:italic>p<\/jats:italic>\u00a0=\u20090.003). This study provides evidence for benefits of pre\u2010symptomatic diagnosis and appropriate therapeutic management, highlighting the need for systematic newborn screening for MTHFR deficiency and pre\u2010symptomatic treatment that may improve outcome.<\/jats:p>","DOI":"10.1002\/jimd.12504","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T07:00:30Z","timestamp":1650697230000},"page":"848-861","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Influence of early identification and therapy on long\u2010term outcomes in early\u2010onset <scp>MTHFR<\/scp> deficiency"],"prefix":"10.1002","volume":"45","author":[{"given":"Mathilde","family":"Yverneau","sequence":"first","affiliation":[{"name":"Department of Child and Adolescent Medicine Rennes Hospital  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Leroux","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Medicine Rennes Hospital  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apolline","family":"Imbard","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory, Robert Debr\u00e9 Hospital, APHP  Paris France"},{"name":"Department of Pediatrics, Reference Center for Inborn Error of Metabolism Necker and Robert\u2010Debr\u00e9 Hospital, APHP, Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"LYPSIS, Universit\u00e9 Paris\u2010Saclay  Ch\u00e2tenay\u2010Malabry France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gleich","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine Center for Child and Adolescent Medicine, University Hospital Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Arion","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Caen Hospital  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Moreau","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory, Rennes Hospital  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010C\u00e9cile","family":"Nassogne","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Cliniques Universitaires Saint\u2010Luc, UCLouvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Szymanowski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Estaing Hospital  Clermont\u2010Ferrand France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Tardieu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tours Hospital  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Touati","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Reference Center for Inborn Error of Metabolism Toulouse Hospital  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Bueno","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen del Roc\u00edo  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly A.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Section of Genetics and Metabolism Children's National Health System  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin\u2010Hsiu","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Pediatrics National Taiwan University Hospital, College of Medicine, National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Huemer","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Children's Research Center University Children's Hospital  Z\u00fcrich Switzerland"},{"name":"Department of Paediatrics Landeskrankenhaus Bregenz  Bregenz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Je\u0161ina","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Inherited Metabolic Disorders First Faculty of Medicine, General University Hospital, Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirian C. H.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Radboud University Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"K\u00f6lker","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine Center for Child and Adolescent Medicine, University Hospital Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Ko\u017eich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Inherited Metabolic Disorders First Faculty of Medicine, General University Hospital, Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lavigne","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Angers University Hospital  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan Meldgaard","family":"Lund","sequence":"additional","affiliation":[{"name":"Departments of Paediatrics and Clinical Genetics, Centre for Inherited Metabolic Diseases Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Mochel","sequence":"additional","affiliation":[{"name":"Department of Genetics AP\u2010HP, Piti\u00e9\u2010Salp\u00eatri\u00e8re University Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Morris","sequence":"additional","affiliation":[{"name":"Willink Metabolic Unit, Manchester Centre for Genomic Medicine Manchester University Hospitals NHS Foundation Trust  Manchester"},{"name":"Alder Hey Children's Hospital  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica Ruiz","family":"Pons","sequence":"additional","affiliation":[{"name":"H.U. 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