Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency

Luk, Anderson Dik Wai and Lee, Pamela P. and Mao, Huawei and Chan, Koon Wing and Chen, Xiang Yuan and Chen, Tong Xin and He, Jian Xin and Kechout, Nadia and Suri, Deepti and Tao, Yin Bo and Xu, Yong Bin and Jiang, Li Ping and Liew, Woei Kang and Jirapongsananuruk, Orathai and Daengsuwan, Tassalapa and Gupta, Anju and Singh, Surjit and Rawat, Amit and Abdul Latiff, Amir Hamzah and Lee, Anselm Chi Wai and Shek, Lynette P. and Nguyen, Thi Van Anh and Chin, Tek Jee and Chien, Yin Hsiu and Latiff, Zarina Abdul and Le, Thi Minh Huong and Le, Nguyen Ngoc Quynh and Lee, Bee Wah and Li, Qiang and Raj, Dinesh and Barbouche, Mohamed-Ridha and Thong, Meow Keong and Ang, Maria Carmen D. and Wang, Xiao Chuan and Xu, Chen Guang and Yu, Hai Guo and Yu, Hsin Hui and Lee, Tsz Leung and Yau, Felix Yat Sun and Wong, Wilfred Hing Sang and Tu, Wenwei and Yang, Wangling and Chong, Patrick Chun Yin and Ho, Marco Hok Kung and Lau, Yu Lung (2017) Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency. Frontiers in Immunology, 8. p. 808. ISSN 1664-3224, DOI

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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.

Item Type: Article
Uncontrolled Keywords: severe combined immunodeficiency; family history; candidiasis; absolute lymphocyte count; newborn screening
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 24 Oct 2019 04:25
Last Modified: 23 Dec 2019 04:38

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