Surjit Singh1, Amit Rawat2, Deepti Suri1, Anju Gupta1, Ravinder Garg1, Biman Saikia3, Ranjana Walker Minz3, Shobha Sehgal3, Koon-Wing Chan4, Yu Lung Lau4, Chikako Kamae5, Kenichi Honma5, Noriko Nakagawa5, Kohsuke Imai5, Shigeaki Nonoyama5, Koichi Oshima6, Noriko Mitsuiki6, Osamu Ohara6. 1. Pediatric Allergy and Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India. 2. Pediatric Allergy and Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address: rawatamit@yahoo.com. 3. Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. 4. Department of Pediatrics and Adolescent Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong. 5. Department of Pediatrics, National Defense Medical College, Tokorozawa, Saitama, Japan. 6. Kazusa DNA Research Institute, Kisarazu, Chiba, Japan.
Abstract
BACKGROUND: X-linked agammaglobulinemia (XLA) is an X-linked genetic defect in maturation of B lymphocytes that results in the absence of B lymphocytes in the peripheral blood and profound hypogammaglobulinemia. It is caused by a mutation in the BTK gene located on the X chromosome. There are no large series describing XLA from the developing world. OBJECTIVE: To analyze the clinical features, immunologic and genetic characteristics, and outcomes of 36 patients with XLA diagnosed and managed for a period of 2 decades. METHODS: Diagnosis of XLA was made on the basis of presence of BTK gene mutation or marked reduction of B lymphocytes in peripheral blood with a family history of an affected male relative. The diagnosis was confirmed by genetic mutation studies in 28 patients with 25 unique mutations in the BTK gene. RESULTS: There was a significant delay in diagnosis in most of the patients. The mean (SD) delay in the diagnosis was 4.2 (3.5) years. Point mutations were the most common mutations detected, accounting for 68% of all mutations. Deletions and insertions were also seen in a few cases. Four of the mutations are novel mutations that have not been previously reported. Seven of the 36 patients (19%) were dead at the time of analysis in the present cohort. The mean survival was 137 months (95% confidence interval, 13-163 months). CONCLUSION: The present study is perhaps the largest series of patients with XLA from any developing country so far.
BACKGROUND:X-linked agammaglobulinemia (XLA) is an X-linked genetic defect in maturation of B lymphocytes that results in the absence of B lymphocytes in the peripheral blood and profound hypogammaglobulinemia. It is caused by a mutation in the BTK gene located on the X chromosome. There are no large series describing XLA from the developing world. OBJECTIVE: To analyze the clinical features, immunologic and genetic characteristics, and outcomes of 36 patients with XLA diagnosed and managed for a period of 2 decades. METHODS: Diagnosis of XLA was made on the basis of presence of BTK gene mutation or marked reduction of B lymphocytes in peripheral blood with a family history of an affected male relative. The diagnosis was confirmed by genetic mutation studies in 28 patients with 25 unique mutations in the BTK gene. RESULTS: There was a significant delay in diagnosis in most of the patients. The mean (SD) delay in the diagnosis was 4.2 (3.5) years. Point mutations were the most common mutations detected, accounting for 68% of all mutations. Deletions and insertions were also seen in a few cases. Four of the mutations are novel mutations that have not been previously reported. Seven of the 36 patients (19%) were dead at the time of analysis in the present cohort. The mean survival was 137 months (95% confidence interval, 13-163 months). CONCLUSION: The present study is perhaps the largest series of patients with XLA from any developing country so far.
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