Folate receptor α deficiency : Myelin‐sensitive MRI as a reliable biomarker to monitor the efficacy and long‐term outcome of a new therapeutic approach
Dreha-Kulaczewski, Steffi ; Sahoo, Prativa ; Preusse, Matthias ; Gkalimani, Irini ; Dechent, Peter ; Helms, Gunther LU
; Hofer, Sabine
; Steinfeld, Robert
and Gärtner, Jutta
(2024)
In Journal of Inherited Metabolic Disease
p.1-17
- Abstract
- Cerebral folate transport deficiency, caused by a genetic defect in folate recep-torα, is a devastating neurometabolic disorder that, if untreated, leads to epi-leptic encephalopathy, psychomotor decline and hypomyelination. Currently,there are limited data on effective dosage and duration of treatment, thoughearly diagnosis and therapy with folinic acid appears critical. The aim of thislong-term study was to identify new therapeutic approaches and novel bio-markers for assessing efficacy, focusing on myelin-sensitive MRI. Clinical, bio-chemical, structural and quantitative MRI parameters of seven patients withgenetically confirmed folate receptorαdeficiency were acquired over 13 years.Multimodal MRI approaches comprised MR-spectroscopy... (More)
- Cerebral folate transport deficiency, caused by a genetic defect in folate recep-torα, is a devastating neurometabolic disorder that, if untreated, leads to epi-leptic encephalopathy, psychomotor decline and hypomyelination. Currently,there are limited data on effective dosage and duration of treatment, thoughearly diagnosis and therapy with folinic acid appears critical. The aim of thislong-term study was to identify new therapeutic approaches and novel bio-markers for assessing efficacy, focusing on myelin-sensitive MRI. Clinical, bio-chemical, structural and quantitative MRI parameters of seven patients withgenetically confirmed folate receptorαdeficiency were acquired over 13 years.Multimodal MRI approaches comprised MR-spectroscopy (MRS), magnetiza-tion transfer (MTI) and diffusion tensor imaging (DTI) sequences. Patientsstarted oral treatment immediately following diagnosis or in an interval of upto 2.5 years. Escalation to intravenous and intrathecal administration was per-formed in the absence of effects. Five patients improved, one with a presymp-tomatic start of therapy remained symptom-free, and one with inconsistenttreatment deteriorated. While CSF 5-methyltetrahydrofolate and MRS parame-ters normalized immediately after therapy initiation, myelin-sensitive MTI andDTI measures correlated with gradual clinical improvement and ongoing mye-lination under therapy. Early initiation of treatment at sufficient doses, consid-ering early intrathecal applications, is critical for favorable outcome. Themajority of patients showed clinical improvements that correlated best withMTI parameters, allowing individualized monitoring of myelination recovery.Presymptomatic therapy seems to ensure normal development and warrantsnewborn screening. Furthermore, the quantitative parameters of myelin-sensitive MRI for therapy assessments can now be used for hypomyelinationdisorders in general. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/d289b3da-63d9-41be-a3cd-e825e631915d
- author
- Dreha-Kulaczewski, Steffi
; Sahoo, Prativa
; Preusse, Matthias
; Gkalimani, Irini
; Dechent, Peter
; Helms, Gunther
LU
; Hofer, Sabine
; Steinfeld, Robert
and Gärtner, Jutta
- organization
- publishing date
- 2024-01-10
- type
- Contribution to journal
- publication status
- epub
- subject
- keywords
- biomarker, cerebral folate deficiency, folate receptorαdeficiency, folate therapy, hypomyelination, leukodystrophy, myelin MRI
- in
- Journal of Inherited Metabolic Disease
- pages
- 1 - 17
- publisher
- Springer
- external identifiers
-
- pmid:38200656
- scopus:85181873710
- ISSN
- 0141-8955
- DOI
- 10.1002/jimd.12713
- language
- English
- LU publication?
- yes
- id
- d289b3da-63d9-41be-a3cd-e825e631915d
- date added to LUP
- 2024-01-12 14:47:07
- date last changed
- 2024-02-09 04:05:49
@article{d289b3da-63d9-41be-a3cd-e825e631915d,
abstract = {{Cerebral folate transport deficiency, caused by a genetic defect in folate recep-torα, is a devastating neurometabolic disorder that, if untreated, leads to epi-leptic encephalopathy, psychomotor decline and hypomyelination. Currently,there are limited data on effective dosage and duration of treatment, thoughearly diagnosis and therapy with folinic acid appears critical. The aim of thislong-term study was to identify new therapeutic approaches and novel bio-markers for assessing efficacy, focusing on myelin-sensitive MRI. Clinical, bio-chemical, structural and quantitative MRI parameters of seven patients withgenetically confirmed folate receptorαdeficiency were acquired over 13 years.Multimodal MRI approaches comprised MR-spectroscopy (MRS), magnetiza-tion transfer (MTI) and diffusion tensor imaging (DTI) sequences. Patientsstarted oral treatment immediately following diagnosis or in an interval of upto 2.5 years. Escalation to intravenous and intrathecal administration was per-formed in the absence of effects. Five patients improved, one with a presymp-tomatic start of therapy remained symptom-free, and one with inconsistenttreatment deteriorated. While CSF 5-methyltetrahydrofolate and MRS parame-ters normalized immediately after therapy initiation, myelin-sensitive MTI andDTI measures correlated with gradual clinical improvement and ongoing mye-lination under therapy. Early initiation of treatment at sufficient doses, consid-ering early intrathecal applications, is critical for favorable outcome. Themajority of patients showed clinical improvements that correlated best withMTI parameters, allowing individualized monitoring of myelination recovery.Presymptomatic therapy seems to ensure normal development and warrantsnewborn screening. Furthermore, the quantitative parameters of myelin-sensitive MRI for therapy assessments can now be used for hypomyelinationdisorders in general.}},
author = {{Dreha-Kulaczewski, Steffi and Sahoo, Prativa and Preusse, Matthias and Gkalimani, Irini and Dechent, Peter and Helms, Gunther and Hofer, Sabine and Steinfeld, Robert and Gärtner, Jutta}},
issn = {{0141-8955}},
keywords = {{biomarker; cerebral folate deficiency; folate receptorαdeficiency; folate therapy; hypomyelination; leukodystrophy; myelin MRI}},
language = {{eng}},
month = {{01}},
pages = {{1--17}},
publisher = {{Springer}},
series = {{Journal of Inherited Metabolic Disease}},
title = {{Folate receptor α deficiency : Myelin‐sensitive MRI as a reliable biomarker to monitor the efficacy and long‐term outcome of a new therapeutic approach}},
url = {{http://dx.doi.org/10.1002/jimd.12713}},
doi = {{10.1002/jimd.12713}},
year = {{2024}},
}