Clinical spectrum of X-linked hyper-IgM syndrome

J Pediatr. 1997 Jul;131(1 Pt 1):47-54. doi: 10.1016/s0022-3476(97)70123-9.


We report the clinical and immunologic features and outcome in 56 patients with X-linked hyper-IgM syndrome, a disorder caused by mutations in the CD40 ligand gene. Upper and lower respiratory tract infections (the latter frequently caused by Pneumocystis carinii), chronic diarrhea, and liver involvement (both often associated with Cryptosporidium infection) were common. Many patients had chronic neutropenia associated with oral and rectal ulcers. The marked prevalence of infections caused by intracellular pathogens suggests some degree of impairment of cell-mediated immunity. Although lymphocyte counts and in vitro proliferation to mitogens were normal, a defective in vitro proliferative response to antigens was observed in some patients, and additional defects of cell-mediated immunity may be presumed on the basis of current knowledge of CD40-ligand function. All patients received regular infusions of immunoglobulins. Four patients underwent liver transplantation because of sclerosing cholangitis, which relapsed in there. Three patients underwent bone marrow transplantation. Thirteen patients (23%) died of infection and/or liver disease. X-linked hyper-IgM syndrome, once considered a clinical variant of hypogammaglobulinemia, is a severe immunodeficiency with significant cellular involvement and a high mortality rate.

MeSH terms

  • Bone Marrow Transplantation
  • CD40 Antigens / genetics
  • Cause of Death
  • Child
  • Child, Preschool
  • Chronic Disease
  • Cryptosporidiosis / physiopathology
  • Diarrhea / physiopathology
  • Genetic Linkage*
  • Humans
  • Hypergammaglobulinemia / genetics*
  • Hypergammaglobulinemia / immunology
  • Hypergammaglobulinemia / physiopathology
  • Hypergammaglobulinemia / therapy
  • Immunity, Cellular / genetics
  • Immunity, Cellular / physiology
  • Immunoglobulin M* / administration & dosage
  • Immunoglobulin M* / therapeutic use
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Deficiency Syndromes / physiopathology
  • Immunologic Deficiency Syndromes / therapy
  • Infant
  • Infant, Newborn
  • Ligands
  • Liver Diseases / physiopathology
  • Liver Transplantation
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Mutation / genetics
  • Neutropenia / physiopathology
  • Opportunistic Infections / physiopathology
  • Oral Ulcer / physiopathology
  • Pneumonia, Pneumocystis / physiopathology
  • Rectal Diseases / physiopathology
  • Respiratory Tract Infections / physiopathology
  • Treatment Outcome
  • Ulcer / physiopathology
  • X Chromosome* / genetics


  • CD40 Antigens
  • Immunoglobulin M
  • Ligands