Influence of early identification and therapy on long-term outcomes in early-onset MTHFR deficiency.
EHOD
MTHFR deficiency
homocystinuria
neurodevelopmental outcome
newborn screening
remethylation defects
Journal
Journal of inherited metabolic disease
ISSN: 1573-2665
Titre abrégé: J Inherit Metab Dis
Pays: United States
ID NLM: 7910918
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
revised:
12
04
2022
received:
13
01
2022
accepted:
21
04
2022
pubmed:
24
4
2022
medline:
20
7
2022
entrez:
23
4
2022
Statut:
ppublish
Résumé
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.
Substances chimiques
Homocysteine
0LVT1QZ0BA
MTHFR protein, human
EC 1.5.1.20
Methylenetetrahydrofolate Reductase (NADPH2)
EC 1.5.1.20
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
848-861Investigateurs
Ana Maria Martins
(AM)
Javier Blasco Alonso
(JB)
Brigitte Chabrol
(B)
Ellen Crushell
(E)
Carlo Dionisi-Vici
(C)
Stephanie Grünewald
(S)
Karine Mention
(K)
Helen Mundy
(H)
Elaine Murphy
(E)
Pilar Quijada Fraile
(PQ)
Carlos José Ruiz
(CJ)
Maria Ángeles Ruiz Gómez
(MÁ)
Saikat Santra
(S)
Thomas Scherer
(T)
Collette Stainforth
(C)
Karolina M Stepien
(KM)
Gere Sunder-Plassmann
(G)
Johan L K Van Hove
(JLK)
Informations de copyright
© 2022 SSIEM.
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