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CASE REPORT article
Front. Pediatr.
Sec. Genetics of Common and Rare Diseases
Volume 12 - 2024 |
doi: 10.3389/fped.2024.1434209
Case report: Cerebral folate deficiency caused by FOLR1 variant
Provisionally accepted- 1 West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, China
- 2 Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, China
Background: Cerebral folate transport deficiency (CFD) is a rare neurological disease characterized by a deficiency in 5-methyltetrahydrofolate (5-MTHF) in the cerebrospinal fluid, with a normal peripheral total folate level. Late infantile-onset refractory seizures, ataxia, movement disorders, hypotonia, developmental delays, and developmental regression characterize CFD. Some patients present with visual and hearing impairments and autism-like manifestations. This study aimed to elucidate the clinical features, diagnostic approach, and therapeutic outcomes in siblings with CFD due to FOLR1 variants, highlighting the importance of early diagnosis and treatment. Case presentation: We reported the cases of two siblings with CFD caused by a new variant in FOLR1. They presented with intractable epilepsy, developmental regression, and ataxia, and the younger sibling developed autism. Whole-exon sequencing revealed a c.148G>A homozygous variant, resulting in a change in the amino acid sequence (p.Glu50Lys). Low 5-MTHF levels were detected in the cerebrospinal fluid. Conclusions: This report illustrates that CFD was caused by FOLR1 variants in two siblings. They had intractable epilepsy, developmental regression, and ataxia, and a diagnosis of CFD was confirmed by a c.148G>A (p.Glu50Lys) variant in FOLR1, a new pathogenic variant in FOLR1. Early diagnosis is essential and can improve outcomes in affected patients. 1 Background Cerebral folate transport deficiency (CFD) is a rare autosomal recessive genetic disease caused by a deficiency of 5-methyltetrahydrofolate (5-MTHF) in the cerebrospinal fluid (CSF), leading to various
Keywords: cerebral folate deficiency, FOLR1 gene variant, 5-MTHF, developmental delay, Seizures
Received: 17 May 2024; Accepted: 28 Aug 2024.
Copyright: © 2024 Wang, Yang, Yu, Deng, Wen, Yang, Liu and Luo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Rong Luo, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
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