Cerebral folate deficiency (CFD) is a rare progressive neurological condition characterized by normal blood folate level and low 5-methyltetrahydrofolate (5-MTHF) levels in the cerebrospinal fluid. Patients present with different neurological findings including hypotonia and microcephaly. Later, patients develop ataxia, seizures, para or quadri-plagia. Herein, we report two siblings; born to consanguineous parents; who had normal neurological development in early childhood. Subsequently they developed drug-resistant seizures, neurological regression, and spastic quadriplegia. After thorough investigations patients had brain MRI which showed abnormal white matter signals and ventricular dilatation, CSF with low 5-MTHF, and whole exome sequencing (WES) revealed a novel homozygous variant in FOLR1 (c.245A > G; p.Tyr82Cys) consistent with the diagnosis of cerebral folate deficiency. They were treated with folinic acid in addition to standard anti-seizure medications. WES aids in reaching CFD diagnosis due to FOLR1 pathogenic variants. These results can be used for future counselling to prevent recurrence in future pregnancies by preimplantation genetic testing prior to implanting the embryo in the uterus. Treatment with folinic acid was shown to improve the neurological symptoms namely reduced the seizures and spasticity.
Keywords: Cerebral folate deficiency; FOLR1 mutation; Folinic acid; Whole exome sequencing.
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