Objective:

To describe an atypical neurological presentation of X linked Lymphoproliferative disease (XLP) in a 5-year-old boy who presented with refractory seizures, encephalopathy, and cerebral edema, with diagnosis confirmed by postmortem genetic analysis.

Background:

XLP is a rare primary immunodeficiency caused by mutations in the SH2D1A gene, which encodes SLAM-associated protein (SAP), critical for immune regulation. XLP primarily affects males and predisposes to severe immune dysregulation, particularly following Epstein-Barr virus infection. While XLP typically manifests as hemophagocytic lymphohistiocytosis, lymphoma, or severe infectious mononucleosis, neurological involvement is less commonly recognized and may pose significant diagnostic challenges.

Design/Methods:

This is a single-patient case report with postmortem neuropathological and genetic analysis.

Results:

A 5-year-old boy presented with a one-month history of high-grade fever, headache, and vomiting, followed by refractory generalized and focal seizures progressing to status epilepticus and altered sensorium. On admission, neurological examination revealed a Glasgow Coma Scale score of 6, bilateral extensor posturing, non-reactive pupils, and left hemiparesis. Cerebrospinal fluid analysis showed lymphocytic pleocytosis, elevated protein, normal glucose, and low adenosine deaminase, effectively excluding tuberculous meningitis. Brain MRI demonstrated multiple T2-FLAIR hyperintensities diffusely involving bilateral cortical regions with contrast enhancement, significant right-sided edema, and midline shift. Despite management, the patient succumbed 12 hours after admission. Postmortem neuropathological examination revealed histiocytic and lymphocytic infiltration without identifiable organisms. Genetic testing on brain biopsy tissue identified a pathogenic SH2D1A mutation, confirming XLP.

Conclusions:

This case highlights a rare and fatal neurological presentation of XLP characterized by refractory seizures, encephalopathy, and diffuse cerebral edema. The postmortem diagnosis underscores the importance of maintaining a high index of suspicion for primary immunodeficiencies in children with unexplained encephalopathy and refractory seizures. Early incorporation of genetic testing in the diagnostic workup may facilitate timely diagnosis and potentially life-saving interventions such as hematopoietic stem cell transplantation.