Here, we report on a male infant with low serum
IgG,
IgA and
IgM levels who suffered from Pneumocystis jirovecii and cytomegalovirus (CMV)
pneumonia. The patient was tested to be HIV-negative. Absolute and relative numbers of lymphocyte subsets were normal, excluding the diagnosis of an X-linked agammaglobulinaemia (Bruton's disease). Despite the decreased serum
IgM level, an
X-linked hyper-IgM syndrome (X-HIGM) was considered. X-HIGM is a rare immunodeficiency usually characterised by recurrent severe
opportunistic infections, low serum
IgG and
IgA, but normal or increased serum
IgM. The syndrome is caused by mutations of the
CD40 ligand (
CD40L) gene. In our patient,
CD40L mutation analysis proved a novel mutation at
codon 257 associated with non-detectable expression of
CD40L on the surface of activated T cells. A literature search revealed that approximately 6.4% of X-HIGM patients had been found to have low serum
IgM levels. Our statistical analysis of the
IgM levels as reported by different studies arouses suspicion that many patients with low
IgM levels may not have undergone diagnostic procedures for X-HIGM. In summary, in this report and critical review of the literature, we described a new mutation of
CD40L and highlighted the pitfalls of the diagnosis of X-HIGM.