De novo mutation in the BTK gene of atypical X-linked agammaglobulinemia in a patient with recurrent pyoderma.
BACKGROUND
X-linked agammaglobulinemia (XLA), characterized by a profound deficiency of all immunoglobulins and the absence of mature B cells, is caused by mutations in the gene encoding Bruton tyrosine kinase (BTK). Most patients have recurrent sinopulmonary infection. Infections usually occur in multiple locations across time, but single infection may be limited to one anatomic location.


OBJECTIVE
To report a case of atypical XLA with recurrent pyoderma and to observe the immunologic changes in the patient in 10 years.


METHODS
Immunologic investigations, skin wound culture, and molecular study with DNA sequencing were performed.


RESULTS
The patient was originally diagnosed as having common variable immunodeficiency disease because of the presence of circulating B cells (CD19+ B cells: 7%) at 11 years old. On further evaluation at the age of 20 years, flow cytometric analysis of lymphocytes showed only 0.4% B cells. The molecular study with DNA sequencing of the patient showed a point mutation in complementary DNA 1630 A>G(p.R544G) in the BTK gene, indicating that the patient has XLA. The mutation analysis of the BTK gene revealed a normal DNA sequence in the other family members.


CONCLUSIONS
This case is an important example of a possible presentation of XLA with a predominant skin manifestation, and it demonstrates that maintaining a high level of clinical suspicion is essential for the diagnosis of XLA in a child with recurrent pyoderma.
Lin
Mao-Tsair
MT
Section of Pediatric Allergy and Immunology, Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.
Chien
Yin-Hsiu
YH
Shyur
Shyh-Dar
SD
Huang
Li-Hsin
LH
Chiang
Yi-Chi
YC
Wen
Da-Chin
DC
Liang
Pei-Hsuan
PH
Yang
Hwai-Chih
HC
D000293:Adolescent; D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000150:complications / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002648:Child; D017074:Common Variable Immunodeficiency / Q000473:pathology; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005434:Flow Cytometry; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011711:Pyoderma / Q000209:etiology*; D012008:Recurrence
D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human