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

Yu Kobayashi, Jun Tohyama, Tomoyuki Akiyama, Shinichi Magara, Hideshi Kawashima, Noriyuki Akasaka, Mitsuko Nakashima, Hirotomo Saitsu, Naomichi Matsumoto

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)266-270
Number of pages5
JournalBrain and Development
Issue number3
Publication statusPublished - Mar 1 2017


  • Cerebral folate deficiency
  • Cortical insult
  • FOLR1
  • Folinic acid therapy
  • Leukoencephalopathy
  • Peripheral neuropathy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology


Dive into the research topics of 'Severe leukoencephalopathy with cortical involvement and peripheral neuropathy due to FOLR1 deficiency'. Together they form a unique fingerprint.

Cite this