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Case Reports
. 2021 Oct-Dec;16(4):273-276.
doi: 10.4103/jpn.JPN_76_20. Epub 2021 Jul 12.

Treatable Neurodegenerative Disorder: Cerebral Folate Transport Deficiency--Two Children from Southern India

Vykuntaraju K Gowda  1 , Balamurugan Natarajan  1 , Varunvenkat M Srinivasan  1 , Sanjay K Shivappa  2
Affiliations
Case Reports

Treatable Neurodegenerative Disorder: Cerebral Folate Transport Deficiency--Two Children from Southern India

Vykuntaraju K Gowda et al. J Pediatr Neurosci. 2021 Oct-Dec.

Abstract

Cerebral folate transport deficiency results from impaired folate transport across the blood:choroid plexus:cerebrospinal fluid (CSF) barrier. This leads to low CSF 5-methyltetrahydrofolate (5MTHF), the active folate metabolite. We are reporting two children with this treatable cerebral folate transport deficiency. Case 1: Seventeen-year-old boy presented with delayed milestones followed by regression, seizures, and intention tremors. On examination child had pyramidal and cerebellar signs. Magnetic resonance imaging (MRI) of brain revealed diffuse cerebral and cerebellar atrophy. Targeted next generation sequencing revealed homozygous missense pathogenic variant in FOLR1 gene in exon 4 c.382C>T p.R128W, confirming the diagnosis of cerebral folate deficiency. Case 2: Six-year-old male child presented with delayed milestones, myoclonic jerks and cognitive regression from 3 years of age. Child had microcephaly with ataxia. Computed tomography (CT) of brain revealed multifocal calcifications. MRI brain revealed cerebellar atrophy with hyperintense T2 signal changes in the subcortical white matter of frontal and temporal lobes. Genetic testing revealed homozygous variant (c.493+2_493+6delTGAGG) in intron 4 of the FOLR1 gene which is a novel pathogenic variant. Both children started on folinic acid and there was a significant improvement in development, behavior, ataxia, and decrease in seizure frequency. In conclusion, cerebral folate transport deficiency should be suspected in every child with global developmental delay, epilepsy, ataxia and neuroimaging showing cerebellar atrophy and calcification. Response to folinic acid supplementation is partial if diagnosed late and treatment initiation is delayed.

Keywords: Cerebral transport defect; FOLR1; folic acid; folinic acid.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
CT scan brain (A and B) showing calcification with corresponding gradient MR image (C) showing presence of blooming (black arrow). MRI T2 WI axial (D and E) showing hyperintensity in subcortical white matter of frontal (black arrow) and temporal lobe (white arrow). T1WI IR images (F) show cerebellar atrophy with prominent folia
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