Severe leukoencephalopathy with cortical involvement and peripheral neuropathy due to FOLR1 deficiency

Brain Dev. 2017 Mar;39(3):266-270. doi: 10.1016/j.braindev.2016.09.011. Epub 2016 Oct 12.


Cerebral folate deficiency due to folate receptor 1 gene (FOLR1) mutations is an autosomal recessive disorder resulting from a brain-specific folate transport defect. It is characterized by late infantile onset, severe psychomotor regression, epilepsy, and leukodystrophy. We describe a consanguineous girl exhibiting severe developmental regression, intractable epilepsy, polyneuropathy, and profound hypomyelination with cortical involvement. Magnetic resonance imaging showed cortical disturbances in addition to profound hypomyelination and cerebellar atrophy. Nerve conduction studies revealed both axonal degeneration and demyelinating features. A diagnosis of cerebral folate deficiency was confirmed by a homozygous c.466T>G (p.W156G) mutation in FOLR1, coupled with extremely low cerebrospinal fluid levels of 5-methyltetrahydrofolate. Her symptoms, neuroradiological findings, and polyneuropathy were alleviated by oral folinic acid treatment in conjunction with intravenous and intramuscular administration therapy. Our patient shows that folinic acid therapy can ameliorate the clinical symptoms, white matter disturbances, cortical insults, and peripheral neuropathy of cerebral folate deficiency caused by FOLR1 mutation. It is important to recognize these clinical symptoms and make a precise diagnosis early on, because cerebral folate deficiency is treatable.

Keywords: Cerebral folate deficiency; Cortical insult; FOLR1; Folinic acid therapy; Leukoencephalopathy; Peripheral neuropathy.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Epilepsy / complications
  • Epilepsy / genetics
  • Female
  • Folate Receptor 1 / deficiency
  • Folate Receptor 1 / metabolism*
  • Folic Acid Deficiency / diagnosis
  • Folic Acid Deficiency / genetics*
  • Humans
  • Leukoencephalopathies / diagnosis
  • Leukoencephalopathies / genetics*
  • Leukoencephalopathies / pathology
  • Magnetic Resonance Imaging / methods
  • Mutation / genetics*
  • Peripheral Nervous System Diseases / diagnosis
  • Peripheral Nervous System Diseases / genetics*
  • Peripheral Nervous System Diseases / pathology


  • FOLR1 protein, human
  • Folate Receptor 1