Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: Data from the E-HOD registry.

Détails

ID Serval
serval:BIB_D06F42D28EF4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: Data from the E-HOD registry.
Périodique
Journal of inherited metabolic disease
Auteur⸱e⸱s
Huemer M., Diodato D., Martinelli D., Olivieri G., Blom H., Gleich F., Kölker S., Kožich V., Morris A.A., Seifert B., Froese D.S., Baumgartner M.R., Dionisi-Vici C., Martin C.A., Baethmann M., Ballhausen D., Blasco-Alonso J., Boy N., Bueno M., Burgos Peláez R., Cerone R., Chabrol B., Chapman K.A., Couce M.L., Crushell E., Dalmau Serra J., Diogo L., Ficicioglu C., García Jimenez M.C., García Silva M.T., Gaspar A.M., Gautschi M., González-Lamuño D., Gouveia S., Grünewald S., Hendriksz C., Janssen MCH, Jesina P., Koch J., Konstantopoulou V., Lavigne C., Lund A.M., Martins E.G., Meavilla Olivas S., Mention K., Mochel F., Mundy H., Murphy E., Paquay S., Pedrón-Giner C., Ruiz Gómez M.A., Santra S., Schiff M., Schwartz I.V., Scholl-Bürgi S., Servais A., Skouma A., Tran C., Vives Piñera I., Walter J., Weisfeld-Adams J.
Collaborateur⸱rice⸱s
EHOD consortium
ISSN
1573-2665 (Electronic)
ISSN-L
0141-8955
Statut éditorial
Publié
Date de publication
03/2019
Peer-reviewed
Oui
Volume
42
Numéro
2
Pages
333-352
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
To explore the clinical presentation, course, treatment and impact of early treatment in patients with remethylation disorders from the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD) international web-based registry.
This review comprises 238 patients (cobalamin C defect n = 161; methylenetetrahydrofolate reductase deficiency n = 50; cobalamin G defect n = 11; cobalamin E defect n = 10; cobalamin D defect n = 5; and cobalamin J defect n = 1) from 47 centres for whom the E-HOD registry includes, as a minimum, data on medical history and enrolment visit. The duration of observation was 127 patient years. In 181 clinically diagnosed patients, the median age at presentation was 30 days (range 1 day to 42 years) and the median age at diagnosis was 3.7 months (range 3 days to 56 years). Seventy-five percent of pre-clinically diagnosed patients with cobalamin C disease became symptomatic within the first 15 days of life. Total homocysteine (tHcy), amino acids and urinary methylmalonic acid (MMA) were the most frequently assessed disease markers; confirmatory diagnostics were mainly molecular genetic studies. Remethylation disorders are multisystem diseases dominated by neurological and eye disease and failure to thrive. In this cohort, mortality, thromboembolic, psychiatric and renal disease were rarer than reported elsewhere. Early treatment correlates with lower overall morbidity but is less effective in preventing eye disease and cognitive impairment. The wide variation in treatment hampers the evaluation of particular therapeutic modalities.
Treatment improves the clinical course of remethylation disorders and reduces morbidity, especially if started early, but neurocognitive and eye symptoms are less responsive. Current treatment is highly variable. This study has the inevitable limitations of a retrospective, registry-based design.
Mots-clé
Adolescent, Adult, Age of Onset, Amino Acid Metabolism, Inborn Errors/diagnosis, Amino Acid Metabolism, Inborn Errors/therapy, Child, Child, Preschool, Cross-Sectional Studies, Disease Progression, Europe, Female, Homocystinuria/metabolism, Humans, Infant, Infant, Newborn, Male, Methylation, Methylenetetrahydrofolate Reductase (NADPH2)/deficiency, Methylenetetrahydrofolate Reductase (NADPH2)/metabolism, Methylmalonic Acid/urine, Muscle Spasticity/metabolism, Phenotype, Pregnancy, Psychotic Disorders/metabolism, Registries, Retrospective Studies, Vitamin B 12/metabolism, Young Adult
Pubmed
Web of science
Création de la notice
10/09/2018 14:26
Dernière modification de la notice
25/03/2023 7:46
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