Folate receptor α deficiency : Myelin‐sensitive MRI as a reliable biomarker to monitor the efficacy and long‐term outcome of a new therapeutic approach

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

Nyckelord

biomarker

cerebral folate deficiency

folate receptorαdeficiency

folate therapy

hypomyelination

leukodystrophy

myelin MRI

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)