Identifying compound heterozygous variants in the EEFSEC gene linked to progressive cerebellar atrophy.

Selenium, an essential micronutrient integrated into selenoproteins as selenocysteine, is fundamental to human health. These selenoproteins are vital for several physiological functions, including maintaining redox balance, safeguarding DNA, and metabolizing thyroid hormones, and are produced via complex pathways involving Sec-tRNA^[Ser]Sec, the SECIS element, and specific proteins such as eEFSec. This study investigates a 4-year-old girl with global developmental delay and cerebellar atrophy, revealing compound heterozygous variants in the EEFSEC gene (p.V488Dfs*113 and p.R443P) through extensive genetic analysis and whole exome sequencing. Both functional prediction tools and structural analysis underscored the detrimental impact of the p.R443P variant. Notably, the patient's plasma exhibited elevated levels of oxidized fatty acid metabolites compared to those in healthy controls, suggesting an impairment in antioxidant mechanisms. This case link a human disease directly to variants in the EEFSEC gene, emphasizing its vital role in cerebellar atrophy and the broader implications for genetic disorders related to defects in selenoprotein synthesis. The results highlight the significance of genetic screening for EEFSEC variants in similar cases, potentially broadening the spectrum of known genetic subtypes associated with selenoprotein translation abnormalities.