Abstract
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of hyperinflammation. It is categorized into a primary or secondary form. Familial HLH is considered a subset of primary HLH that results from a biallelic mutation in one of the four genes that regulate granule-dependent cytotoxicity: PRF1, UNC13D, STX11, and STXBP2. The reported ocular findings in association with HLH are diverse and variable, with few reports in particular in patients with primary HLH. As far as our knowledge goes, this is the first documented instance of a genetically confirmed case of PRF1-associated familial HLH with this specific presentation. CASE PRESENTATION: A previously healthy 11-year-old boy presented with a one-week history of acute esotropia. A dilated fundus exam revealed peripheral snowballs with multiple areas of perivascular sheathing bilaterally with corresponding focal vascular leakage on fundus fluorescein angiography (FFA). Complete systemic workup, including brain magnetic resonance imaging (MRI), showed hyperintensities involving brain parenchyma, cerebellum, and a short spinal cord segment. The neurological exam and lumbar puncture results were within normal at that time. However, later on, the patient presented with progressively worsening systemic manifestations, including ataxic gait, dysarthria, and upper and lower limb weakness. Multiple treatment regimens were initiated without significant improvement, including intravenous methylprednisolone, intravenous immunoglobulins, and plasma exchange. Whole-exome sequencing (WES) revealed a pathogenic homozygous missense mutation (c.1081 A > T p.(Arg361Trp)) in the PRF1 gene, confirming the diagnosis of familial hemophagocytic lymphohistiocytosis. HLH treatment protocol was initiated, and the patient was transferred to another center for a hematopoietic stem cell transplantation (HSCT). CONCLUSION: This report describes a case of PRF1-associated familial HLH with unusual initial ocular presentation, highlighting the importance of a thorough systemic workup and the consideration of this rare diagnosis for such findings.