title: Severe leukoencephalopathy with cortical involvement and peripheral neuropathy due to FOLR1 deficiency.
abstract: 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.
authors.affiliation: Department of Child Neurology, Nishi-Niigata Chuo National Hospital, Japan. Electronic address: u-kb@masa.go.jp.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Child Neurology, Nishi-Niigata Chuo National Hospital, Japan; Niigata University Medical and Dental Hospital, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Tohyama
authors.affiliation: Department of Child Neurology, Okayama University Hospital, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: Department of Child Neurology, Nishi-Niigata Chuo National Hospital, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Magara
authors.affiliation: Department of Child Neurology, Nishi-Niigata Chuo National Hospital, Japan.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Kawashima
authors.affiliation: Department of Child Neurology, Nishi-Niigata Chuo National Hospital, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Akasaka
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D002648:Child; D004827:Epilepsy / Q000150:complications / Q000235:genetics; D005260:Female; D058975:Folate Receptor 1 / Q000172:deficiency / Q000378:metabolism*; D005494:Folic Acid Deficiency / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D056784:Leukoencephalopathies / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D009154:Mutation / Q000235:genetics*; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: C548696:FOLR1 protein, human; D058975:Folate Receptor 1
keywords: Cerebral folate deficiency; Cortical insult; FOLR1; Folinic acid therapy; Leukoencephalopathy; Peripheral neuropathy