title: 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.affiliation: From United States Immune Deficiency Network (JAW, MCM, CCR, HDO), the Immune Deficiency Foundation (JAW, MCM), the Johns Hopkins University School of Medicine (JAW, HML), the University of Arkansas for Medical Sciences (SMJ, AWB), the University of Pennsylvania School of Medicine (KS), the University of Tennessee School of Medicine (MEC), the Mt Sinai School of Medicine (CCR), and the University of Washington School of Medicine (HDO).
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Winkelstein
authors.forename: Mary C
authors.initials: MC
authors.lastname: Marino
authors.forename: Howard M
authors.initials: HM
authors.lastname: Lederman
authors.forename: Stacie M
authors.initials: SM
authors.lastname: Jones
authors.forename: Kathleen
authors.initials: K
authors.lastname: Sullivan
authors.forename: A Wesley
authors.initials: AW
authors.lastname: Burks
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Conley
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cunningham-Rundles
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology*; D017668:Age of Onset; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012042:Registries; D014481:United States / Q000453:epidemiology