X-linked agammaglobulinemia: Twenty years of single-center experience from North West India.
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.



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.



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.



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).



The present study is perhaps the largest series of patients with XLA from any developing country so far.
Pediatric Allergy and Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Surjit
S
Singh
Pediatric Allergy and Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address: rawatamit@yahoo.com.
Amit
A
Rawat
Pediatric Allergy and Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Deepti
D
Suri
Pediatric Allergy and Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Anju
A
Gupta
Pediatric Allergy and Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Ravinder
R
Garg
Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Biman
B
Saikia
Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Ranjana Walker
RW
Minz
Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Shobha
S
Sehgal
Department of Pediatrics and Adolescent Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
Koon-Wing
KW
Chan
Department of Pediatrics and Adolescent Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
Yu Lung
YL
Lau
Department of Pediatrics, National Defense Medical College, Tokorozawa, Saitama, Japan.
Chikako
C
Kamae
Department of Pediatrics, National Defense Medical College, Tokorozawa, Saitama, Japan.
Kenichi
K
Honma
Department of Pediatrics, National Defense Medical College, Tokorozawa, Saitama, Japan.
Noriko
N
Nakagawa
Department of Pediatrics, National Defense Medical College, Tokorozawa, Saitama, Japan.
Kohsuke
K
Imai
Department of Pediatrics, National Defense Medical College, Tokorozawa, Saitama, Japan.
Shigeaki
S
Nonoyama
Kazusa DNA Research Institute, Kisarazu, Chiba, Japan.
Koichi
K
Oshima
Kazusa DNA Research Institute, Kisarazu, Chiba, Japan.
Noriko
N
Mitsuiki
Kazusa DNA Research Institute, Kisarazu, Chiba, Japan.
Osamu
O
Ohara
D000293:Adolescent; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001772:Blood Cell Count; D002648:Child; D002675:Child, Preschool; D040181:Genetic Diseases, X-Linked / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D005838:Genotype; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007194:India; D007223:Infant; D053208:Kaplan-Meier Estimate; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D009154:Mutation; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism
D007136:Immunoglobulins; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human