FOLR1 Gene Variation With Adult-Onset Cerebral Folate Deficiency and Stable Clinical and MRI Features up to 2 Years

Neurology: Genetics · 7 authors, 1 centre

AI SUMMARY

FIDELITY 100%

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

This case report describes a 47-year-old man presenting with double vision and postural instability.

Full summary

467 CHARS

This case report describes a 47-year-old man presenting with double vision and postural instability. Brain MRI showed bilateral, symmetric white matter hyperintensities, and diffusion tensor imaging revealed reduced fractional anisotropy. Asymptomatic family members were found to be carriers of these variants. The authors suggest these specific variants may weaken, but not eliminate, folate receptor-α function, explaining the atypical, mild adult-onset phenotype.

STUDY TYPE

case_report

SPECIALTY

neurology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10629229

FOLR1 Gene Variation With Adult-Onset Cerebral Folate Deficiency and Stable Clinical and MRI Features up to 2 Years

Neurology: Genetics

READ THE FULL PAPER

ABSTRACT

Abstract Objectives The objective of this case report was to describe the first report of FOLR1 variants associated with adult-onset paucisymptomatic leukoencephalopathy associated with cerebral folate deficiency (CFD). Methods Considering the patient's symptoms, a nonprogressive leukoencephalopathy was suspected. CSF 5-methyltetrahydrofolate levels were low (10 nmol/L, normal range 41–117). With no other identifiable causes, a genetic analysis was conducted, revealing a compound heterozygous FOLR1 variation (c.45G>T and c. 493+2T>C). Results A 47-year-old man with a history of drug and alcohol abuse was admitted to the hospital for double vision and postural instability. MRI of the brain was performed, which showed bilateral leukoencephalopathy. Diffusion tensor imaging revealed a diffuse reduction in fractional anisotropy, suggesting microstructural changes. MRI of the brain and overall clinical picture were stable on subsequent serial examinations. Discussion Scientific evidence supports the deleterious effect of c.45G>T and c.493+2T>C variations on the folate receptor-α (FRα) protein structure and function. The weakness of the expression and function of FRα without elimination of its function caused by specific compound heterozygous variations may explain the atypical features observed in our patient. Although rare, CFD should be considered in paucisymptomatic adult patients with stable diffuse MRI white matter changes.

CITATION EXPORT

Carlo Manco, Rosa Cortese, Manfredi Alberti et al.. FOLR1 Gene Variation With Adult-Onset Cerebral Folate Deficiency and Stable Clinical and MRI Features up to 2 Years. Neurology: Genetics. (2023). https://doi.org/10.1212/NXG.0000000000200104

AUTHORS

7 · 1 CENTRES

Carlo Manco, Rosa Cortese, Manfredi Alberti, Silvia Bianchi, Lucia Monti, Nicola De Stefano, Carla Battisti

1From the Centre for Precision and Translational Medicine (C.M., R.C., S.B., N.D.S., C.B.), Department of Medicine, Surgery and Neuroscience, University of Siena; Neurology Unit (M.A.), Department of Neurology and Human Movement Sciences, University Hospital of Siena; Department of Medical, Surgical and Neurological Science (M.A.), University of Siena; and Diagnostic and Functional Neuroimaging Unit (L.M.), Department of Neurology and Human Movement Sciences, University Hospital of Siena, Italy.