Enteroviral meningoencephalitis as a complication of X-linked hyper IgM syndrome

We describe 5 children from 2 families with mutations in the CD40 ligand (C D40L) gene leading to absent expression of CD40L on activated CD4 cells. Al l subjects presented with interstitial pneumonia with low serum IgG and nor mal serum IgM. One child had normal and one child had elevated serum IgA. F our had confirmed Pneumocystis carinii pneumonia. In spite of intravenous i mmunoglobulin treatment yielding therapeutic serum immunoglobulin levels, 3 children had enteroviral encephalitis. When assessed by flow cytometry, th e 3 surviving affected male children had absent CD40L expression on activat ed CD4(+) T cells. The affected children from both families were shown to h ave the same single nucleotide insertion (codon 131) resulting in frameshif t and early termination within exon 4 (extracellular domain). This observat ion demonstrates that persistent enteroviral infection is not only observed in X-linked agammaglobulinemia but may also occur in patients with X-linke d hyper IgM syndrome.