X-linked agammaglobulinemia

Individuals who have a rare genetic immune system disorder that prevents them from making antibodies nevertheless appear to be moderately healthy and lead productive lives, according to results of a study by investigators at St. Jude Children's Research Hospital.

A report on this study appears in the current online edition of Clinical Immunology.

The study of 41 adults with X-linked agammaglobulinemia (XLA) showed that they can function as relatively healthy, productive individuals, even though they remain vulnerable to chronic, low-grade infections. These individuals had a mean age of 4 years (range 1 month to 53 years) when their diseases were diagnosed; and 27 of the patients had family histories of XLA. The study was based on results of a questionnaire filled out by each participant concerning current and past medical problems and quality of life.

"Until we did this study, there was almost nothing in the medical literature about adults with XLA," said Mary Ellen Conley, M.D., a member of the Department of Immunology at St. Jude and senior author of the report. "In fact, old reports we read stated that the vast majority of these patients have chronic lung disease by age 15. We and other physicians were quite surprised at how well these patients are doing with the proper care."

XLA is a rare disease that is inherited through a mutation in the Btk gene on the X-chromosome--one of the two types of sex chromosomes. Males with this disease have very low levels of infection-fighting proteins called antibodies. Treatment includes aggressive use of antibiotics and replacement of the missing antibodies with gamma globulin.

"Almost all of the adults with XLA had chronic medical problems; however, these problems did not interfere with normal daily activities, and the quality of life in this group was equivalent to that of the general male population of the United States," said Vanessa Howard, R.N., M.S.N., a nurse practitioner for the Immunology service at St. Jude and first author of the paper. "In the past, the majority of patients with XLA died of acute or chronic infections in the first two decades of life," Howard noted. "But in the last 20 years the outlook for patients with XLA has significantly improved, thanks to earlier diagnosis and improved gamma globulin therapy. Our study is reassuring and helps to put into perspective the ability of such patients to thrive with proper care, despite this potentially devastating disease."

Forty of the 41 patients were receiving intravenous infusions of gamma globulin every two to four weeks and 16 (39 percent) were taking chronic (long-term) antibiotics in order to prevent infections, the St. Jude team reported.

In addition, 17 patients (41 percent) had not been hospitalized for infection since diagnosis and 28 (68 percent) had not been hospitalized in the past five years. Moreover, 34 (83 percent) of these patients rated their health as good, very good or excellent; 35 (86 percent) of patients missed fewer than 10 days of work or school due to illness in the past year; and 18 (44 percent) reported they had not missed any work or school.

Thirteen of the 41 patients reported that they had chronic lung disease, and 33 indicated that they had one or more episodes of sinusitis in the preceding year. Other diseases that were common but not debilitating among this group were arthritis, diarrhea and skin infections.

Several factors may have contributed to the increased survival of this group of patients. When compared to all patients with XLA, a high percentage of the patients included in this study had mild mutations in Btk. In addition, most had older brothers or cousins with XLA. Thus, they were probably diagnosed earlier and treated more aggressively.

Other authors of the study include Mehmet Kocak (St. Jude); Jeffrey M. Green (Children's Hospital of Philadelphia); Savita Pahwa (University of Miami School of Medicine, Fla.); Jerry A. Winkelstein (The Johns Hopkins University School of Medicine; Baltimore, Md.); and John M. Boyle (SRBI; Silver Spring, Md.).