Recurrent pneumonia with mild hypogammaglobulinemia diagnosed as X-linked agammaglobulinemia in adults.
BACKGROUND
X-linked agammaglobulinemia (XLA) is a humoral immunodeficiency caused by disruption of the Bruton's tyrosine kinase (BTK) gene. Typical XLA patients suffer recurrent and severe bacterial infections in childhood.


METHODS
Flow cytometric analysis of the peripheral monocytes using the anti-BTK antibody was used to characterize a 27 year old male patient with mild hypogammaglobulinemia (IgG, 635 mg/dl; IgM, 11 mg/dl; IgA, <5 mg/dl). He had suffered from frequent pneumonia since age 25 but had no history of frequent infections in his childhood or in adolescence. Sequencing of the BTK cDNA obtained from an Epstein-Barr virus-transformed B lymphoblastoid cell line derived from the bone marrow of the patient was performed to confirm a genetic defect.


RESULTS
Flow cytometric analysis of cytoplasmic BTK protein in peripheral monocytes indicated that the patient presents a rare case of adult-onset XLA and that his mother is an XLA carrier. Sequencing of the BTK gene revealed a deletion of AG in the codon for Glu605 (AGT), resulting in an aberrant stop codon that truncates the BTK protein in its kinase domain.


CONCLUSIONS
This case suggests that some XLA cases may remain undiagnosed because they only show mild hypogammaglobulinemia and they lack repeated infections in childhood. Flow cytometric analysis is a powerful method to screen these patients.
Usui
K
K
Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan.
Sasahara
Y
Y
Tazawa
R
R
Hagiwara
K
K
Tsukada
S
S
Miyawaki
T
T
Tsuchiya
S
S
Nukiwa
T
T
D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000175:diagnosis* / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005434:Flow Cytometry; D017353:Gene Deletion; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D009000:Monocytes / Q000201:enzymology; D009154:Mutation; D010375:Pedigree; D011014:Pneumonia / Q000150:complications*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D014960:X Chromosome
D018076:DNA, Complementary; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human