Case Report: Cerebral folate deficiency caused by FOLR1 variant

Qian Wang; Jie Yang; Chunmei Yu; Yao Deng; Qianhui Wen; Hua Yang; Hao Liu; Rong Luo

doi:10.3389/fped.2024.1434209

Case Report: Cerebral folate deficiency caused by FOLR1 variant

Front Pediatr. 2024 Sep 12:12:1434209. doi: 10.3389/fped.2024.1434209. eCollection 2024.

Authors

Qian Wang^{1

2}, Jie Yang^{1

2}, Chunmei Yu^{1

2}, Yao Deng^{1

2}, Qianhui Wen^{1

2}, Hua Yang^{1

2}, Hao Liu^{1

2}, Rong Luo^{1

2}

Affiliations

¹ Department of Pediatric Neurology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
² Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, Sichuan University, Chengdu, Sichuan, China.

Abstract

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.

Keywords: 5-MTHF; FOLR1 gene variant; cerebral folate deficiency; developmental delay; seizures.

Publication types

Case Reports

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the National Key R&D Program of China (No. 2021YFC1005305) and the Sichuan Province Science and Technology Support Program (No. 2023NSFSC1492).