Cystathionine β‐synthase deficiency in the E‐HOD registry‐part I: pyridoxine responsiveness as a determinant of biochemical and clinical phenotype at diagnosis. Issue 3 (28th December 2020)

• Record Type: Journal Article
• Authors: Kožich, Viktor; Sokolová, Jitka; Morris, Andrew A. M.; Pavlíková, Markéta; Gleich, Florian; Kölker, Stefan; Krijt, Jakub; Dionisi‐Vici, Carlo; Baumgartner, Matthias R.; Blom, Henk J.; Huemer, Martina
• Other Names: Aldámiz‐Echevarría Luis investigator.; Arantes Rodrigo Rezende investigator.; Arrieta Francisco investigator.; Blasco‐Alonso Javier investigator.; Brouwers Martijn investigator.; Brunner‐Krainz Michaela investigator.; Bueno María investigator.; Peláez Rosa Burgos investigator.; Cano Aline investigator.; Couce María‐Luz investigator.; Crushell Ellen investigator.; Ficicioglu Can investigator.; Forny Patrick investigator.; García Jiménez María Concepción investigator.; Gaspar Ana investigator.; González‐Lamuño Leguina Domingo investigator.; Chapman Kimberly A. investigator.; Chien Yin‐Hsiu investigator.; Janssen Mirian C.H. investigator.; Ješina Pavel investigator.; Lachmann Robin investigator.; Lavigne Christian investigator.; Lund Allan M. investigator.; Lüsebrink Natalia investigator.; Maillot Francois investigator.; Martins Ana Maria investigator.; Olivas Silvia Meavilla investigator.; Mention Karine investigator.; Mochel Fanny investigator.; Monavari Ahmad investigator.; Moreira Sónia investigator.; Moreno Carolina Araujo investigator.; Muačević‐Katanec Diana investigator.; Mundy Helen investigator.; Murphy Elaine investigator.; Olivieri Giorgia investigator.; Paquay Stéphanie investigator.; Pedrón‐Giner Consuelo investigator.; Quintana Luís Peña investigator.; Porras‐Hurtado Gloria L. investigator.; Fraile Pilar Quijada investigator.; Redonnet‐Vernhet Isabelle investigator.; Rennings Alexander J.M. investigator.; Pons Mònica Ruiz investigator.; Santra Saikat investigator.; Servais Aude investigator.; Schiaffino Maria Cristina investigator.; Schiff Manuel investigator.; Schwahn Bernd C. investigator.; Schwartz Ida V.D. investigator.; Sremba Leighann J. investigator.; Stainforth Collette investigator.; Stepien Karolina M. investigator.; Sykut‐Cegielska Jolanta investigator.; Terry Allyson investigator.; Tran Christel investigator.; Miñana Isidro Vitoria investigator.; Vives‐Piñera Inmaculada investigator.; Williams Monique investigator.; Zeman Jiří investigator.; Zielonka Matthias investigator.;
• Is Part Of: Journal of inherited metabolic disease. Volume 44:Issue 3(2021)
• Page Start: 677
• Page End: 692
• Publication Date: 2020-12-28
• Subjects: homocystinuria -- patient registry -- natural history -- methionine -- thromboembolism -- developmental delay; Metabolism, Inborn errors of -- Periodicals; Metabolism -- Disorders -- Periodicals; 616.39042
• DOI: 10.1002/jimd.12338
• Languages: English
• ISSNs: 0141-8955

Abstract

Abstract: Cystathionine β‐synthase (CBS) deficiency has a wide clinical spectrum, ranging from neurodevelopmental problems, lens dislocation and marfanoid features in early childhood to adult onset disease with predominantly thromboembolic complications. We have analysed clinical and laboratory data at the time of diagnosis in 328 patients with CBS deficiency from the E‐HOD (European network and registry for Homocystinurias and methylation Defects) registry. We developed comprehensive criteria to classify patients into four groups of pyridoxine responsivity: non‐responders (NR), partial, full and extreme responders (PR, FR and ER, respectively). All groups showed overlapping concentrations of plasma total homocysteine while pyridoxine responsiveness inversely correlated with plasma/serum methionine concentrations. The FR and ER groups had a later age of onset and diagnosis and a longer diagnostic delay than NR and PR patients. Lens dislocation was common in all groups except ER but the age of dislocation increased with increasing responsiveness. Developmental delay was commonest in the NR group while no ER patient had cognitive impairment. Thromboembolism was the commonest presenting feature in ER patients, whereas it was least likely at presentation in the NR group. This probably is due to the differences in ages at presentation: all groups had a similar number of thromboembolic events per 1000 patient‐years. Clinical severity of CBS deficiency depends on the degree of pyridoxine responsiveness. Therefore, a standardised pyridoxine‐responsiveness test in newly diagnosed patients and a critical review of previous assessments is indispensable to ensure adequate therapy and to prevent or reduce long‐term complications.