Family history of early infant death correlates with earlier age at diagnosis but not shorter time to diagnosis for severe combined immunodeficiency

Anderson Dik Wai LukPamela P. LeeHuawei MaoKoon Wing ChanXiang Yuan ChenTong Xin ChenJian Xin HeNadia KechoutDeepti SuriYin Bo TaoYong Bin XuLi Ping JiangWoei Kang LiewOrathai JirapongsananurukTassalapa DaengsuwanAnju GuptaSurjit SinghAmit RawatAmir Hamzah Abdul LatiffAnselm Chi Wai LeeLynette P. ShekThi Van Anh NguyenTek Jee ChinYin Hsiu ChienZarina Abdul LatiffThi Minh Huong LeNguyen Ngoc Quynh LeBee Wah LeeQiang LiDinesh RajMohamed Ridha BarboucheMeow Keong ThongMaria Carmen D. AngXiao Chuan WangChen Guang XuHai Guo YuHsin Hui YuTsz Leung LeeFelix Yat Sun YauWilfred Hing Sang WongWenwei TuWangling YangPatrick Chun Yin ChongMarco Hok Kung HoYu Lung LauThe University of Hong KongGuangzhou Children's HospitalShanghai Jiao Tong University School of MedicineBeijing Children's HospitalInstitut Pasteur - AlgerPostgraduate Institute of Medical Education and ResearchGuangzhou Women and Children's Medical CenterChongqing Medical UniversityKK Women's And Children's HospitalMahidol UniversityQueen Sirikit National Institute of Child HealthMonash University MalaysiaMount Elizabeth Medical CentreNational University of SingaporeNational Children's HospitalSarawak General HospitalNational Taiwan UniversityUniversiti Kebangsaan MalaysiaSichuan Second West China HospitalHoly Family HospitalUniversity of Tunis El ManarUniversity of MalayaSan Pedro HospitalShanghai Children's Medical CenterSun Yat-Sen UniversityNanjing Children's HospitalQueen Elizabeth Hospital Hong Kong2018-12-212019-03-142018-12-212019-03-142017-07-12Frontiers in Immunology. Vol.8, No.JUL (2017)166432242-s2.0-85023170610https://repository.li.mahidol.ac.th/handle/20.500.14594/42820© 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. 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-Guérin (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.Mahidol UniversityImmunology and MicrobiologyFamily history of early infant death correlates with earlier age at diagnosis but not shorter time to diagnosis for severe combined immunodeficiencyArticleSCOPUS10.3389/fimmu.2017.00808