First case report of cerebral folate deficiency caused by a novel mutation of FOLR1 gene in a Chinese patient
Open Access
- 26 November 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Medical Genetics
- Vol. 21 (1), 1-5
- https://doi.org/10.1186/s12881-020-01162-3
Abstract
Cerebral folate deficiency (CFD) is a neurological disease, hallmarked by remarkable low concentrations of 5-methyltetrahydrofolic acid (5-MTHF) in cerebrospinal fluid (CSF). The primary causes of CFD include the presence of folate receptor (FR) autoantibodies, defects of FR encoding gene FOLR1, mitochondrial diseases and congenital abnormalities in folate metabolism. Here we first present a Chinese male CFD patient whose seizure onset at 2 years old with convulsive status epilepticus. Magnetic Resonance Imaging (MRI) revealed the development of encephalomalacia, laminar necrosis in multiple lobes of the brain and cerebellar atrophy. Whole Exome Sequencing (WES) uncovered a homozygous missense variant of c.524G > T (p.C175F) in FOLR1 gene. Further laboratory tests demonstrated the extremely low level of 5-MTHF in the CSF from this patient, which was attributed to cerebral folate transport deficiency. Following the intravenous and oral treatment of calcium folinate, the concentrations of 5-MTHF in CSF were recovered to the normal range and seizure symptoms were relieved as well. One novel variation of FOLR1 was firstly identified from a Chinese male patient with tonic-clonic seizures, developmental delay, and ataxia. The WES and laboratory results elucidated the etiology of the symptoms. Clinical outcomes were improved by early diagnosis and proper treatment.Keywords
Funding Information
- National Natural Science Foundation of China (81801297, 81771408)
- Hunan Provincial Science and Technology Department (No. 2020JJ5946)
This publication has 20 references indexed in Scilit:
- Structural basis for molecular recognition of folic acid by folate receptorsNature, 2013
- Molecular characterization of folate receptor 1 mutations delineates cerebral folate transport deficiencyBrain, 2012
- Pyridoxal phosphate-responsive seizures in a patient with cerebral folate deficiency (CFD) and congenital deafness with labyrinthine aplasia, microtia and microdontia (LAMM)Molecular Genetics and Metabolism, 2011
- The etiologic classification of epilepsyEpilepsia, 2011
- Progressive ataxia and myoclonic epilepsy in a patient with a homozygous mutation in the FOLR1 geneJournal of Inherited Metabolic Disease, 2010
- CONGENITAL NULL MUTATIONS OF THE FOLR1 GENE: A PROGRESSIVE NEUROLOGIC DISEASE AND ITS TREATMENTNeurology, 2009
- Folate Receptor Alpha Defect Causes Cerebral Folate Transport Deficiency: A Treatable Neurodegenerative Disorder Associated with Disturbed Myelin MetabolismAmerican Journal of Human Genetics, 2009
- Cerebrospinal Fluid Concentrations of Folate, Biogenic Amines and Pterins in Rett Syndrome: Treatment with Folinic AcidNeuropediatrics, 2005
- Cerebral folate deficiencyDevelopmental Medicine and Child Neurology, 2004
- Cerebral folate deficiencyDevelopmental Medicine and Child Neurology, 2004