A Novel Case of Pediatric CMV Encephalitis, Encephalopathy, and Brain Infarction in a Child With Homozygous CARMIL2 Splice‑Site Mutation: Case Report and Review of the Literature

Abstract

Biallelic loss-of-function variants in CARMIL2/RLTPR impair CD28-mediated T-cell costimulation and cause a combined immunodeficiency with variable infectious and inflammatory phenotypes. CNS viral disease and cerebrovascular complications are sparsely documented in this setting.

Here, we are reporting an eight-year-old Saudi girl of consanguineous parentage presented with febrile illness, rapid-onset encephalopathy, focal deficits, and refractory focal seizures. Neuroimaging showed diffuse atrophy with cortical/subcortical T2/FLAIR hyperintensities and features compatible with ischemic injury. CSF PCR detected CMV DNA. Immunology revealed leukopenia/lymphopenia with normal quantitative immunoglobulins but abnormal T/B/NK subsets. Whole-exome sequencing identified homozygous splice‑site variants CARMIL2 (NM_001013838.2:c.958+1G>A) and PRMT7 (NM_001290018.1:c.282+1G>A). She received ganciclovir with corticosteroids/IVIg and antiseizure therapy; partial stabilization was followed by protracted encephalopathy and death from severe chest infection and respiratory failure one year later.

Conclusions: This fatal case supports CARMIL2 deficiency as a predisposing condition for severe CMV CNS disease and cerebrovascular injury in children. Early recognition of inborn errors of immunity (IEI) in pediatric encephalitis—especially in consanguineous populations—may enable timely antivirals, tailored immunomodulation, consideration of HSCT in selected phenotypes, and informed genetic counseling.