AUTHOR=Luk Anderson Dik Wai , Lee Pamela P. , Mao Huawei , Chan Koon-Wing , Chen Xiang Yuan , Chen Tong-Xin , He Jian Xin , Kechout Nadia , Suri Deepti , Tao Yin Bo , Xu Yong Bin , Jiang Li Ping , Liew Woei Kang , Jirapongsananuruk Orathai , Daengsuwan Tassalapa , Gupta Anju , Singh Surjit , Rawat Amit , Abdul Latiff Amir Hamzah , Lee Anselm Chi Wai , Shek Lynette P. , Nguyen Thi Van Anh , Chin Tek Jee , Chien Yin Hsiu , Latiff Zarina Abdul , Le Thi Minh Huong , Le Nguyen Ngoc Quynh , Lee Bee Wah , Li Qiang , Raj Dinesh , Barbouche Mohamed-Ridha , Thong Meow-Keong , Ang Maria Carmen D. , Wang Xiao Chuan , Xu Chen Guang , Yu Hai Guo , Yu Hsin-Hui , Lee Tsz Leung , Yau Felix Yat Sun , Wong Wilfred Hing-Sang , Tu Wenwei , Yang Wangling , Chong Patrick Chun Yin , Ho Marco Hok Kung , Lau Yu Lung 

TITLE=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

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00808

DOI=10.3389/fimmu.2017.00808

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Background</title><p>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.</p></sec><sec id="ST2"><title>Objective</title><p>The aim of this study was to identify the clinical features that affect age at diagnosis (AD) and time to the diagnosis of SCID.</p></sec><sec id="ST3"><title>Methods</title><p>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.</p></sec><sec id="ST4"><title>Results</title><p>A total of 88 different SCID gene mutations were identified in 94 patients, including 49 <italic>IL2RG</italic> mutations, 12 <italic>RAG1</italic> mutations, 8 <italic>RAG2</italic> mutations, 7 <italic>JAK3</italic> mutations, 4 <italic>DCLRE1C</italic> mutations, 4 <italic>IL7R</italic> mutations, 2 <italic>RFXANK</italic> mutations, and 2 <italic>ADA</italic> 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 (<italic>n</italic> = 57). A total of 29 patients had a positive FH. Candidiasis (<italic>n</italic> = 27) and bacillus Calmette–Guérin (BCG) vaccine infection (<italic>n</italic> = 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 × 10<sup>9</sup>/L with over 88% patients below 3 × 10<sup>9</sup>/L. Positive FH was associated with earlier AP by 1 month (<italic>p</italic> = 0.002) and diagnosis by 2 months (<italic>p</italic> = 0.008), but not shorter time to diagnosis (<italic>p</italic> = 0.494). Candidiasis was associated with later AD by 2 months (<italic>p</italic> = 0.008) and longer time to diagnosis by 0.55 months (<italic>p</italic> = 0.003). BCG infections were not associated with age or time to diagnosis.</p></sec><sec id="ST5"><title>Conclusion</title><p>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 × 10<sup>9</sup>/L.</p></sec>