Cystathionine β-synthase deficiency in the E-HOD registry-part I: pyridoxine responsiveness as a determinant of biochemical and clinical phenotype at diagnosis.

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State: Public
Version: author
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_7F1B6C75347C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cystathionine β-synthase deficiency in the E-HOD registry-part I: pyridoxine responsiveness as a determinant of biochemical and clinical phenotype at diagnosis.
Journal
Journal of inherited metabolic disease
Author(s)
Kožich V., Sokolová J., Morris AAM, Pavlíková M., Gleich F., Kölker S., Krijt J., Dionisi-Vici C., Baumgartner M.R., Blom H.J., Huemer M.
Working group(s)
E-HOD consortium
Contributor(s)
Aldámiz-Echevarría L., Arantes R.R., Arrieta F., Blasco-Alonso J., Brouwers M., Brunner-Krainz M., Bueno M., Peláez R.B., Cano A., Couce M.L., Crushell E., Ficicioglu C., Forny P., García Jiménez M.C., Gaspar A., González-Lamuño Leguina D., Chapman K.A., Chien Y.H., Janssen MCH, Ješina P., Lachmann R., Lavigne C., Lund A.M., Lüsebrink N., Maillot F., Martins A.M., Olivas S.M., Mention K., Mochel F., Monavari A., Moreira S., Moreno C.A., Muačević-Katanec D., Mundy H., Murphy E., Olivieri G., Paquay S., Pedrón-Giner C., Quintana L.P., Porras-Hurtado G.L., Fraile P.Q., Redonnet-Vernhet I., Rennings AJM, Pons M.R., Santra S., Servais A., Schiaffino M.C., Schiff M., Schwahn B.C., Schwartz IVD, Sremba L.J., Stainforth C., Stepien K.M., Sykut-Cegielska J., Terry A., Tran C., Miñana I.V., Vives-Piñera I., Williams M., Zeman J., Zielonka M.
ISSN
1573-2665 (Electronic)
ISSN-L
0141-8955
Publication state
Published
Issued date
05/2021
Peer-reviewed
Oui
Volume
44
Number
3
Pages
677-692
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
developmental delay, homocystinuria, methionine, natural history, patient registry, thromboembolism
Pubmed
Web of science
Open Access
Yes
Create date
28/10/2021 7:51
Last modification date
29/10/2021 5:41
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