X-linked hyper-IgM syndrome (CD40L deficiency)

Patients with XHIM have recurrent bacterial and opportunistic infections starting in the first year of life. Pneumocystis Carinii pneumonia is a common presenting infection. Other patients may have chronic, profuse diarrhea requiring parenteral nutrition. Over 50% of patients have chronic or intermittent neutropenia, often associated with oral ulcers. Cryptosporidium infection may lead to severe bile duct disease and hepatic cancer. Serum concentration of IgG is usually less than 200 mg/dl; IgM may be low, normal or elevated. Atypical cases may present with recurrent infections, anemia or hepatitis in the second or third decade of life. XHIM has a higher risk of malignancy than other antibody deficiencies. Lymphomas affect patients with XHIM as they do patients with common variable immunodeficiency (CVID), but the incidence of adenocarcinomas of the liver and biliary track is particularly high; these latter malignancies are suspected to be related to the high incidence of viral hepatitis. Diarrhea and cholangitis are caused by Cryptosporidium.

Therapeutic options