TY - JOUR
T1 - Wiskott Aldrich Syndrome
T2 - A Multi-Institutional Experience From India
AU - Suri, Deepti
AU - Rikhi, Rashmi
AU - Jindal, Ankur K.
AU - Rawat, Amit
AU - Sudhakar, Murugan
AU - Vignesh, Pandiarajan
AU - Gupta, Anju
AU - Kaur, Anit
AU - Sharma, Jyoti
AU - Ahluwalia, Jasmina
AU - Bhatia, Prateek
AU - Khadwal, Alka
AU - Raj, Revathi
AU - Uppuluri, Ramya
AU - Desai, Mukesh
AU - Taur, Prasad
AU - Pandrowala, Ambreen A.
AU - Gowri, Vijaya
AU - Madkaikar, Manisha R.
AU - Lashkari, Harsha Prasada
AU - Bhattad, Sagar
AU - Kumar, Harish
AU - Verma, Sanjeev
AU - Imai, Kohsuke
AU - Nonoyama, Shigeaki
AU - Ohara, Osamu
AU - Chan, Koon W.
AU - Lee, Pamela P.
AU - Lau, Yu Lung
AU - Singh, Surjit
N1 - Funding Information:
This work was supported by India Council of Medical Research (ICMR), New Delhi, India, and Department of Health Research,
Funding Information:
The authors gratefully acknowledge the support provided by the Indian Council of Medical Research (ICMR), New Delhi, India and Department of Biotechnology, Ministry of Science and Technology, Government of India for funds for the study (vide Grant No. ICMR GIA/48/2014-DHR/3.6 and DBT/PR26412/ MED/12/792/2017); Foundation of Primary Immunodeficiency Diseases (FPID), United States of America; Prof. Sudhir Gupta, Professor of Medicine, Pathology & Laboratory Medicine, and Microbiology & Molecular Genetics, University of California at Irvine, Irvine, CA, United States of America. We thankfully acknowledge State Governments of Punjab, Haryana, Delhi, Himachal Pradesh; Kusum Arora Memorial Trust, Sukhmani Foundation; Pediatric Medical Support Society; God’s Child Foundation and Veeranwali Foundation Nanhi-Jaan for their generous financial support to a large number of children in this cohort. This financial support has helped in providing regular IVIg therapy to some of the patients in the present cohort. We sincerely acknowledge support of Drs. Jean Delaunay, Chrystèle Bilhou-Nabera and Alexis Proust at Service Hématologie, Immunologie et de Cytogénétique, Hôpital de Bicêtre, Le Kremlin Bicêtre, France in carrying out genetic analysis in our initial patients. We do acknowledge the resident doctors involved in patient care of this cohort over a period of 10 years.
Publisher Copyright:
© Copyright © 2021 Suri, Rikhi, Jindal, Rawat, Sudhakar, Vignesh, Gupta, Kaur, Sharma, Ahluwalia, Bhatia, Khadwal, Raj, Uppuluri, Desai, Taur, Pandrowala, Gowri, Madkaikar, Lashkari, Bhattad, Kumar, Verma, Imai, Nonoyama, Ohara, Chan, Lee, Lau and Singh.
PY - 2021/4/16
Y1 - 2021/4/16
N2 - Background: Wiskott Aldrich syndrome (WAS) is characterized by bleeding manifestations, recurrent infections, eczema, autoimmunity, and malignancy. Over the last decade, improved awareness and better in-house diagnostic facilities at several centers in India has resulted in increased recognition of WAS. This study reports collated data across major primary immunodeficiency diseases (PID) centers in India that are involved in care of children with WAS and highlights the varied clinical presentations, genetic profile, and outcomes of patients in India. Methods: Request to share data was sent to multiple centers in India that are involved in care and management of patients with PID. Six centers provided requisite data that were compiled and analyzed. Results: In this multi-institutional cohort, clinical details of 108 patients who had a provisional diagnosis of WAS were received. Of these, 95 patients with ‘definite WAS’ were included Fourteen patients were classified as XLT and 81 patients as WAS. Median age at onset of symptoms of patients was 3 months (IQR 1.6, 6.0 months) and median age at diagnosis was 12 months (IQR 6,48 months). Clinical profile included bleeding episodes (92.6%), infections (84.2%), eczema (78.9%), various autoimmune manifestations (40%), and malignancy (2.1%). DNA analysis revealed 47 variants in 67 cases. Nonsense and missense variants were the most common (28.4% each), followed by small deletions (19.4%), and splice site defects (16.4%). We also report 24 novel variants, most of these being frameshift and nonsense mutations resulting in premature termination of protein synthesis. Prophylactic intravenous immunoglobulin (IVIg) was initiated in 52 patients (54.7%). Hematopoietic stem cell transplantation (HSCT) was carried out in 25 patients (26.3%). Of those transplanted, disease-free survival was seen in 15 patients (60%). Transplant related mortality was 36%. Outcome details were available for 89 patients. Of these, 37% had died till the time of this analysis. Median duration of follow-up was 36 months (range 2 weeks- 12 years; IQR 16.2 months- 70 months). Conclusions: We report the first nationwide cohort of patients with WAS from India. Bleeding episodes and infections are common manifestations. Mortality continues to be high as curative therapy is not accessible to most of our patients.
AB - Background: Wiskott Aldrich syndrome (WAS) is characterized by bleeding manifestations, recurrent infections, eczema, autoimmunity, and malignancy. Over the last decade, improved awareness and better in-house diagnostic facilities at several centers in India has resulted in increased recognition of WAS. This study reports collated data across major primary immunodeficiency diseases (PID) centers in India that are involved in care of children with WAS and highlights the varied clinical presentations, genetic profile, and outcomes of patients in India. Methods: Request to share data was sent to multiple centers in India that are involved in care and management of patients with PID. Six centers provided requisite data that were compiled and analyzed. Results: In this multi-institutional cohort, clinical details of 108 patients who had a provisional diagnosis of WAS were received. Of these, 95 patients with ‘definite WAS’ were included Fourteen patients were classified as XLT and 81 patients as WAS. Median age at onset of symptoms of patients was 3 months (IQR 1.6, 6.0 months) and median age at diagnosis was 12 months (IQR 6,48 months). Clinical profile included bleeding episodes (92.6%), infections (84.2%), eczema (78.9%), various autoimmune manifestations (40%), and malignancy (2.1%). DNA analysis revealed 47 variants in 67 cases. Nonsense and missense variants were the most common (28.4% each), followed by small deletions (19.4%), and splice site defects (16.4%). We also report 24 novel variants, most of these being frameshift and nonsense mutations resulting in premature termination of protein synthesis. Prophylactic intravenous immunoglobulin (IVIg) was initiated in 52 patients (54.7%). Hematopoietic stem cell transplantation (HSCT) was carried out in 25 patients (26.3%). Of those transplanted, disease-free survival was seen in 15 patients (60%). Transplant related mortality was 36%. Outcome details were available for 89 patients. Of these, 37% had died till the time of this analysis. Median duration of follow-up was 36 months (range 2 weeks- 12 years; IQR 16.2 months- 70 months). Conclusions: We report the first nationwide cohort of patients with WAS from India. Bleeding episodes and infections are common manifestations. Mortality continues to be high as curative therapy is not accessible to most of our patients.
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U2 - 10.3389/fimmu.2021.627651
DO - 10.3389/fimmu.2021.627651
M3 - Article
C2 - 33936041
AN - SCOPUS:85105231539
SN - 1664-3224
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 627651
ER -