Xiaojing Li, Yali Chen, Chungui Deng, Dongmei Wang, Jianwu Qiu
In infants with fever and convulsions showing poor response to empirical treatment, cerebrospinal fluid mNGS is strongly recommended for early diagnosis. Further research is needed on the pathogenic role of TLR3 variants.
BACKGROUND: Neonatal herpes simplex virus type 2 (HSV-2) encephalitis frequently manifests with atypical clinical features, which complicates its early identification. Given the challenge of controlling the infant's seizures, whole exome sequencing was conducted to rule out genetic disorders like early-onset epileptic encephalopathy; this process incidentally revealed a variation in the TLR3 gene. Host genetic factors, especially the antiviral pathway mediated by TLR3, may influence disease progression.
CASE PRESENTATION: A 17-day-old female presented with fever and frequent convulsions 15 days after birth. Cranial MRI showed meningoencephalitis, and funduscopy revealed infectious retinopathy. Exome sequencing identified a heterozygous TLR3 variant (c.338A > C, p. Gln113Pro), and cerebrospinal fluid metagenomic sequencing confirmed HSV-2 infection. Initial cefotaxime-sulbactam plus penicillin was ineffective; subsequent acyclovir and immunoglobulin therapy led to gradual improvement.
CONCLUSION: In infants with fever and convulsions showing poor response to empirical treatment, cerebrospinal fluid mNGS is strongly recommended for early diagnosis. Further research is needed on the pathogenic role of TLR3 variants.