Family history of early infant death correlates with earlier age at diagnosis but not shorter time to diagnosis for severe combined immunodeficiency
Journal
Frontiers in Immunology
Journal Volume
8
Journal Issue
JUL
Pages
808
Date Issued
2017
Author(s)
Wai Luk A.D.
Lee P.P.
Mao H.
Chan K.-W.
Chen X.Y.
Chen T.-X.
He J.X.
Kechout N.
Suri D.
Tao Y.B.
Xu Y.B.
Jiang L.P.
Liew W.K.
Jirapongsananuruk O.
Daengsuwan T.
Gupta A.
Singh S.
Rawat A.
Latiff A.H.A.
Lee A.C.W.
Shek L.P.
Nguyen T.V.A.
Chin T.J.
Latiff Z.A.
Le T.M.H.
Le N.N.Q.
Lee B.W.
Li Q.
Raj D.
Barbouche M.-R.
Thong M.-K.
Ang M.C.D.
Wang X.C.
Xu C.G.
Yu H.G.
Lee T.L.
Yau F.Y.S.
Wong W.H.
Tu W.
Yang W.
Chong P.C.Y.
Ho M.H.K.
Lau Y.L.
Abstract
Background: Severe combined immunodeficiency (SCID) is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH) has been associated with earlier diagnosis. Objective: The aim of this study was to identify the clinical features that affect age at diagnosis (AD) and time to the diagnosis of SCID. Methods: From 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP), and AD were selected for study. Results: A total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57). A total of 29 patients had a positive FH. Candidiasis (n = 27) and bacillus Calmette-Gu?rin (BCG) vaccine infection (n = 19) were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC) was 1.05 × 109/L with over 88% patients below 3 × 109/L. Positive FH was associated with earlier AP by 1 month (p = 0.002) and diagnosis by 2 months (p = 0.008), but not shorter time to diagnosis (p = 0.494). Candidiasis was associated with later AD by 2 months (p = 0.008) and longer time to diagnosis by 0.55 months (p = 0.003). BCG infections were not associated with age or time to diagnosis. Conclusion: FH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of SCID were not recognized by clinicians to shorten the time to diagnosis. We suggest that lymphocyte subset should be performed for any infant with one or more of the following four clinical features: FH, candidiasis, BCG infections, and ALC below 3 × 109/L. ? 2017 Luk, Lee, Mao, Chan, Chen, Chen, He, Kechout, Suri, Tao, Xu, Jiang, Liew, Jirapongsananuruk, Daengsuwan, Gupta, Singh, Rawat, Abdul Latiff, Lee, Shek, Nguyen, Chin, Chien, Latiff, Le, Le, Lee, Li, Raj, Barbouche, Thong, Ang, Wang, Xu, Yu, Yu, Lee, Yau, Wong, Tu, Yang, Chong, Ho and Lau.
SDGs
Other Subjects
adenosine deaminase; CD19 antigen; CD3 antigen; Janus kinase 3; RAG1 protein; RAG2 protein; adolescent; adult; age; Article; autosomal recessive severe combined immunodeficiency; B lymphocyte; bovine tuberculosis; candidiasis; child; child death; clinical feature; early diagnosis; failure to thrive; family history; female; gene mutation; genetic analysis; genotype; human; infant; lymphocyte count; major clinical study; male; Mycobacterium bovis BCG; onset age; opportunistic infection; recurrent infection; severe combined immunodeficiency; time to treatment; X linked severe combined immunodeficiency
Publisher
Frontiers Media S.A.
Type
journal article