Y. Chen, S. Rong, H. Luo, B. Huang, F. Hu, M. Chen, et al. (2023). Ketogenic Diet Attenuates Refractory Epilepsy of Harel-Yoon Syndrome With ATAD3A Variants: A Case Report and Review of Literature. Pediatric neurology, 143, 79-83. https://doi.org/10.1016/j.pediatrneurol.2023.03.003

PubMed 37031571

[Abstract]
BACKGROUND: Harel-Yoon syndrome is a disease caused by variants in the ATAD3A gene, which manifest as global developmental delay, hypotonia, intellectual disability, and axonal neuropathy. The aim of this study is to summarize the clinical and gene mutation characteristics of a child with refractory epilepsy caused by ATAD3A gene mutation.

METHODS: The whole-exome sequencing combined with copy number variation analysis could help to understand the genetic diversity and underlying disease mechanisms in ATAD3A gene mutation.

RESULTS: We report a Chinese boy with Harel-Yoon syndrome presenting with refractory epilepsy, hypotonia, global developmental delay, and congenital cataract through whole-exome sequencing. Genetic analysis showed a missense mutation, c.251T>C(p.Thr84Met) in the ATAD3A gene (NM_001170535.1). Further copy number variation analysis identified a novel heterozygous deletion on chromosome1p36.33, which spans ATAD3A exon 1 and 2 regions. Multiple antiepileptic drugs failed to control his seizures. Eventually, seizure was controlled through ketogenic diet (KD).

CONCLUSION: Our case shows the potential diagnostic role of whole-exome sequencing in Harel-Yoon syndrome and expands the ATAD3A gene mutation spectrum. Multiple antiepileptic drugs failed to control refractory epilepsy in Harel-Yoon syndrome. The KD therapy may be effective for patients with refractory epilepsy who carry the ATAD3A variants.