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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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-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.

Original languageEnglish
Article number808
JournalFrontiers in Immunology
Volume8
Issue numberJUL
DOIs
Publication statusPublished - 12 Jul 2017

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Severe Combined Immunodeficiency
Mutation
Candidiasis
Bacillus
Infection
Lymphocyte Count
Patient Selection
Infant Death
Early Diagnosis
X-Linked Combined Immunodeficiency Diseases
BCG Vaccine
Delayed Diagnosis
Lymphocyte Subsets
Hematopoietic Stem Cells

Keywords

  • Absolute lymphocyte count
  • Candidiasis
  • Family history
  • Newborn screening
  • Severe combined immunodeficiency

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Family history of early infant death correlates with earlier age at diagnosis but not shorter time to diagnosis for severe combined immunodeficiency. / Wai Luk, Anderson Dik; 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; Latiff, Amir Hamzah Abdul; Lee, Anselm Chi Wai; Shek, Lynette P.; Nguyen, Thi Van Anh; Chin, Tek Jee; Chien, Yin Hsiu; Abdul Latiff, Zarina; 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.

In: Frontiers in Immunology, Vol. 8, No. JUL, 808, 12.07.2017.

Research output: Contribution to journalArticle

Wai Luk, AD, Lee, PP, Mao, H, Chan, KW, Chen, XY, Chen, TX, He, JX, Kechout, N, Suri, D, Tao, YB, Xu, YB, Jiang, LP, Liew, WK, Jirapongsananuruk, O, Daengsuwan, T, Gupta, A, Singh, S, Rawat, A, Latiff, AHA, Lee, ACW, Shek, LP, Nguyen, TVA, Chin, TJ, Chien, YH, Abdul Latiff, Z, Le, TMH, Le, NNQ, Lee, BW, Li, Q, Raj, D, Barbouche, MR, Thong, MK, Ang, MCD, Wang, XC, Xu, CG, Yu, HG, Yu, HH, Lee, TL, Yau, FYS, Wong, WHS, Tu, W, Yang, W, Chong, PCY, Ho, MHK & Lau, YL 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, vol. 8, no. JUL, 808. https://doi.org/10.3389/fimmu.2017.00808
Wai Luk, Anderson Dik ; 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 ; Latiff, Amir Hamzah Abdul ; Lee, Anselm Chi Wai ; Shek, Lynette P. ; Nguyen, Thi Van Anh ; Chin, Tek Jee ; Chien, Yin Hsiu ; Abdul Latiff, Zarina ; 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. / Family history of early infant death correlates with earlier age at diagnosis but not shorter time to diagnosis for severe combined immunodeficiency. In: Frontiers in Immunology. 2017 ; Vol. 8, No. JUL.
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title = "Family history of early infant death correlates with earlier age at diagnosis but not shorter time to diagnosis for severe combined immunodeficiency",
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{\'e}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.",
keywords = "Absolute lymphocyte count, Candidiasis, Family history, Newborn screening, Severe combined immunodeficiency",
author = "{Wai Luk}, {Anderson Dik} and Lee, {Pamela P.} and Huawei Mao and Chan, {Koon Wing} and Chen, {Xiang Yuan} and Chen, {Tong Xin} and He, {Jian Xin} and Nadia Kechout and Deepti Suri and Tao, {Yin Bo} and Xu, {Yong Bin} and Jiang, {Li Ping} and Liew, {Woei Kang} and Orathai Jirapongsananuruk and Tassalapa Daengsuwan and Anju Gupta and Surjit Singh and Amit Rawat and Latiff, {Amir Hamzah Abdul} and Lee, {Anselm Chi Wai} and Shek, {Lynette P.} and Nguyen, {Thi Van Anh} and Chin, {Tek Jee} and Chien, {Yin Hsiu} and {Abdul Latiff}, Zarina and Le, {Thi Minh Huong} and Le, {Nguyen Ngoc Quynh} and Lee, {Bee Wah} and Qiang Li and Dinesh Raj 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 Wenwei Tu and Wangling Yang and Chong, {Patrick Chun Yin} and Ho, {Marco Hok Kung} and Lau, {Yu Lung}",
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TY - JOUR

T1 - Family history of early infant death correlates with earlier age at diagnosis but not shorter time to diagnosis for severe combined immunodeficiency

AU - Wai Luk, Anderson Dik

AU - Lee, Pamela P.

AU - Mao, Huawei

AU - Chan, Koon Wing

AU - Chen, Xiang Yuan

AU - Chen, Tong Xin

AU - He, Jian Xin

AU - Kechout, Nadia

AU - Suri, Deepti

AU - Tao, Yin Bo

AU - Xu, Yong Bin

AU - Jiang, Li Ping

AU - Liew, Woei Kang

AU - Jirapongsananuruk, Orathai

AU - Daengsuwan, Tassalapa

AU - Gupta, Anju

AU - Singh, Surjit

AU - Rawat, Amit

AU - Latiff, Amir Hamzah Abdul

AU - Lee, Anselm Chi Wai

AU - Shek, Lynette P.

AU - Nguyen, Thi Van Anh

AU - Chin, Tek Jee

AU - Chien, Yin Hsiu

AU - Abdul Latiff, Zarina

AU - Le, Thi Minh Huong

AU - Le, Nguyen Ngoc Quynh

AU - Lee, Bee Wah

AU - Li, Qiang

AU - Raj, Dinesh

AU - Barbouche, Mohamed Ridha

AU - Thong, Meow Keong

AU - Ang, Maria Carmen D.

AU - Wang, Xiao Chuan

AU - Xu, Chen Guang

AU - Yu, Hai Guo

AU - Yu, Hsin Hui

AU - Lee, Tsz Leung

AU - Yau, Felix Yat Sun

AU - Wong, Wilfred Hing Sang

AU - Tu, Wenwei

AU - Yang, Wangling

AU - Chong, Patrick Chun Yin

AU - Ho, Marco Hok Kung

AU - Lau, Yu Lung

PY - 2017/7/12

Y1 - 2017/7/12

N2 - 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.

AB - 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.

KW - Absolute lymphocyte count

KW - Candidiasis

KW - Family history

KW - Newborn screening

KW - Severe combined immunodeficiency

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