Atypical X-linked agammaglobulinaemia caused by a novel BTK mutation in a selective immunoglobulin M deficiency patient.
BACKGROUND
X-linked agammaglobulinaemia (XLA) is the most common inherited humoural immunodeficiency disorder. Mutations in the gene coding for Bruton's tyrosine kinase (BTK) have been identified as the cause of XLA. Most affected patients exhibit a marked reduction of serum immunoglobulins, mature B cells, and an increased susceptibility to recurrent bacterial infections. However, the diagnosis of XLA can be a challenge in certain patients who have near-normal levels of serum immunoglobulin. Furthermore, reports on XLA with renal involvement are scant.


METHODS
We report an atypical XLA patient who presented with selective immunoglobulin M (IgM) immunodeficiency and nephropathy. He was diagnosed with selective IgM immunodeficiency, based on his normal serum immunoglobulin G (IgG) and immunoglobulin A (IgA) levels but undetectable serum IgM level. Intravenous immunoglobulin was initiated due to increased infections and persistent proteinuria but no improvement in proteinuria was found. A lupus-like nephritis was detected in his kidney biopsy and the proteinuria subsided after receiving a mycophenolate mofetil regimen. Although he had a history of recurrent bacterial infections since childhood, XLA was not diagnosed until B-lymphocyte surface antigen studies and a genetic analysis were conducted.


CONCLUSIONS
We suggest that B-lymphocyte surface antigen studies and a BTK mutation analysis should be performed in familial patients with selective IgM deficiency to rule out atypical XLA.
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tze-You First Road, Kaohsiung City 807, Taiwan. 910208@ms.kmuh.org.tw.
Lee-Moay
LM
Lim
Jer-Ming
JM
Chang
I-Fang
IF
Wang
Wei-Chiao
WC
Chang
Daw-Yang
DY
Hwang
Hung-Chun
HC
Chen
D000361:Agammaglobulinemia / Q000175:diagnosis / Q000235:genetics*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis*; D002648:Child; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D007075:Immunoglobulin M / Q000172:deficiency* / Q000235:genetics; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D009393:Nephritis / Q000188:drug therapy / Q000209:etiology; D011507:Proteinuria / Q000209:etiology
D000944:Antigens, Differentiation, B-Lymphocyte; D007075:Immunoglobulin M; D009173:Mycophenolic Acid