ADEM-Like Presentation as the Main Manifestation of X-Linked Lymphoproliferative Disease in a 4-Year-Old Male Patient

Case Study: X-linked lymphoproliferative disease (XLP) is a genetic disorder because of impaired activation of NK- and T-cells and impaired macrophage regulation. XLP often presents with fulminant infectious mononucleosis, dysgammaglobulinemia, and lymphoma or hemophagocytic lymphohistiocytosis (HLH) often affecting the CNS. Here, we present a 4-year-old boy with typical features of ADEM, that is, sudden onset of ataxia, loss of speech, and mental status changes. The MRI of the brain showed hazy, bilateral, and widespread lesions in the white matter, adjacent cortex, and cerebellum. CSF studies revealed mild pleocytosis (8/uL), without malignant cells, or oligoclonal bands. Serum MOG-IgG antibodies were negative. intravenous methylprednisolone (IVMP) was administered for 5 days. The patient left the hospital in an improved condition but was admitted several days later again with ataxia.

A second MRI showed a similar lesion pattern but with widespread contrast medium enhancement. IVMP therapy was repeated but without immediate improvement.

Further medical history revealed that the patient received treatment for abdominal Burkitt lymphoma including intravenous immunoglobulins for hypogammaglobulinemia after administration of Rituximab. His brother had died at the age of 4 years, because of the severe HLH associated with EBV infection.

Although on admission, our patient did not meet criteria for HLH (i.e., fever, splenomegaly, cytopenia, and hypertriglyceridemia), the family history, his B-cell lymphoma, and hypogammaglobulinemia pointed toward XLP. FACS analysis showed signaling lymphocyte activation molecule-associated protein (SAP) deficiency in NK- and T-cells and genetic testing revealed the associated SH2 domain protein 1A gene mutation (SH2D1A).

The patient is being treated with cyclosporine A and dexamethasone while awaiting hematopoietic cell transplantation.

Conclusion: In patients with ADEM-like presentation but limited response to high-dose steroid therapy and subsequent unusual MRI features, other diseases with primary CNS manifestation such as CNS vasculitis or HLH must be taken into consideration.

Keywords: HLH, XLP.