X-linked agammaglobulinemia: report on a United States registry of 201 patients.

Abstract

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in the gene for Bruton tyrosine kinase (BTK) that result in the deficient development of B lymphocytes and hypogammaglobulinemia. Because the disorder is uncommon, no single institution has had sufficient numbers of patients to develop a comprehensive clinical picture of the disorder. Accordingly, a national registry of United States residents with XLA was established in 1999 to provide an updated clinical view of the disorder in a large cohort of patients. A total of 201 patients were registered by 66 physicians. The estimated birth rate for the 10-year period of 1988-1997 was 1/379,000. Infection was the most common initial clinical presentation (85%), followed by a positive family history (41%) and neutropenia (11%). Although the average age of diagnosis was younger in patients with a positive family history (mean, 2.59 yr) than in patients with a negative family history (mean, 5.37 yr) (p < 0.001), only 34.5% of patients with a positive family history at the time of their birth were diagnosed before clinical symptoms developed-that is, based on family history alone. Seventy percent of patients had at least 1 episode of otitis, 62% at least 1 episode of pneumonia, 60% at least 1 episode of sinusitis, 23% at least 1 episode of chronic/recurrent diarrhea, 21% at least 1 episode of conjunctivitis, 18% at least 1 episode of pyoderma and/or cellulitis, 11% at least 1 episode of meningitis/encephalitis, 10% at least 1 episode of sepsis, 8% at least 1 episode of septic arthritis, 6% at least 1 episode of hepatitis, and 3% at least 1 episode of osteomyelitis. Fourteen of 201 (6.9%) patients were dead at the time they were entered in the Registry. However, in a prospective 4 /4-year follow-up of living patients, only 3/80 (3.75%) patients died. Causes of death included disseminated enterovirus infection (n = 6), pulmonary insufficiency (n = 5), adenovirus infection (n = 1), sepsis (n = 1), acquired immunodeficiency disease syndrome (AIDS) (n = 1), myocarditis (n = 1), hepatitis (n = 2), and stem cell transplantation (n = 1).

• Authors: Jerry A Winkelstein, Mary C Marino, Howard M Lederman, Stacie M Jones, Kathleen Sullivan, A Wesley Burks, Mary Ellen Conley, Charlotte Cunningham-Rundles, Hans D Ochs
• Journal: Medicine (Medicine (Baltimore)) Vol. 85 Issue 4 Pg. 193-202 (Jul 2006) ISSN: 0025-7974 [Print] United States
• PMID: 16862044 (Publication Type: Journal Article)

Topics

• Adolescent
• Adult
• Agammaglobulinemia (complications, diagnosis, epidemiology)
• Age of Onset
• Cause of Death
• Child
• Child, Preschool
• Genetic Diseases, X-Linked (complications, diagnosis, epidemiology)
• Humans
• Incidence
• Infant
• Male
• Middle Aged
• Prevalence
• Registries
• United States (epidemiology)