Pattern of inheritance: X-linked (at Xq26)
The family history may show several affected relatives, or patients may have a negative family history.
Clinical features:
(1) The primary feature is recurrent infections, sometimes with opportunistic pathogens
(1a) pneumocystis pneumonia
(1b) upper and lower respiratory tract infections with encapsulated bacteria
(1c) infections by nonencapsulated bacteria
(1d) recurrent viral infections, including CMV, parvovirus and adenovirus, which may be more serious than normal
(1e) opportunistic fungal infections
(1f) Cryptosporidium infections
(2) The onset is often during infancy with diarrhea and a failure to thrive, but other patients may present during childhood, adolescence or early adulthood.
(3) Some patients may develop a degenerative CNS disease.
(4) Some patients may develop arthritis or autoimmune disease.
Laboratory features:
(1) increased IgM, although IgM levels may be low normal or normal at initial presentation
(2) decreased IgG levels
(3) IgA variable, and may be increased
(4) normal number of T and B cells
(5) normal response of lymphocytes to mitogens
(6) persistent or recurrent neutropenia
Molecular defect: mutation in the CD40 ligand (CD154) on the surface of activated T cells
The differential diagnosis includes hyper-IgM syndromes with autosomal dominant, autosomal recessive, and acquired patterns.
