Fulltext

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

Luk ADW 1 , Lee PP 1 , Mao H 1 , Chan KW 1 , Chen XY 2 , Chen TX 3 Show all authors , He JX 4 , Kechout N 5 , Suri D 6 , Tao YB 2 , Xu YB 7 , Jiang LP 8 , Liew WK 9 , Jirapongsananuruk O 10 , Daengsuwan T 11 , Gupta A 6 , Singh S 6 , Rawat A 6 , Abdul Latiff AH 12 , Lee ACW 13 , Shek LP 14 , Nguyen TVA 15 , Chin TJ 16 , Chien YH 17 , Latiff ZA 18 , Le TMH 15 , Le NNQ 15 , Lee BW 14 , Li Q 19 , Raj D 20 , Barbouche MR 21 , Thong MK 22 , Ang MCD 23 , Wang XC 24 , Xu CG 25 , Yu HG 26 , Yu HH 17 , Lee TL 1 , Yau FYS 27 , Wong WH 1 , Tu W 1 , Yang W 1 , Chong PCY 1 , Ho MHK 1 , Lau YL 1

Affiliations 

  • 1 LKS Faculty of Medicine, Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong
  • 2 Guangzhou Children's Hospital, Guangzhou, China
  • 3 Department of Allergy and Immunology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 4 Beijing Children's Hospital, Capital Medical University, Beijing, China
  • 5 Institut Pasteur d'Algérie, Algeria, North Africa
  • 6 Allergy Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
  • 7 Guang Zhou Women and Children's Medical Center, Guangzhou, China
  • 8 Children's Hospital of Chongqing Medical University, Chongqing, China
  • 9 KK Women's and Children's Hospital, Singapore, Singapore
  • 10 Department of Pediatrics, Siriraj Hospital Mahidol University, Bangkok, Thailand
  • 11 Queen Sirikit National Institute of Child Health, Bangkok, Thailand
  • 12 Monash University, Selangor, Malaysia
  • 13 Mount Elizabeth Hospital, Singapore, Singapore
  • 14 National University of Singapore, Singapore, Singapore
  • 15 National Children's Hospital, Hanoi, Vietnam
  • 16 Sarawak General Hospital Malaysia, Kuching, Malaysia
  • 17 National Taiwan University Children's Hospital, Taipei, Taiwan
  • 18 University Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia
  • 19 Sichuan Second West China Hospital, Sichuan, China
  • 20 Department of Paediatrics, Holy Family Hospital, New Delhi, India
  • 21 Department of Immunology, Institut Pasteur de Tunis and University Tunis-El Manar, Tunis, Tunisia
  • 22 Faculty of Medicine, Department of Paediatrics, University of Malaya, Kuala Lumpur, Malaysia
  • 23 San Pedro Hospital, Davao, Philippines
  • 24 Children's Hospital of Fudan University, Shanghai, China
  • 25 The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
  • 26 Nanjing Children's Hospital, Nanjing, China
  • 27 Queen Elizabeth Hospital, Hong Kong, Hong Kong
Front Immunol, 2017;8:808.
PMID: 28747913 DOI: 10.3389/fimmu.2017.00808

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 × 10(9)/L with over 88% patients below 3 × 10(9)/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 × 10(9)/L.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

MeSH terms
Similar publications