The spectrum of primary immunodeficiencies at a tertiary care hospital in Pakistan

Sonia Qureshi; Fatima Mir; Samina Junejo; Khalid Saleem; Samreen Zaidi; Abdullah B Naveed; Khalil Ahmad; Farah Naz Qamar

doi:10.1016/j.waojou.2020.100133

The spectrum of primary immunodeficiencies at a tertiary care hospital in Pakistan

World Allergy Organ J. 2020 Aug 5;13(7):100133. doi: 10.1016/j.waojou.2020.100133. eCollection 2020 Jul.

Authors

Sonia Qureshi¹, Fatima Mir¹, Samina Junejo², Khalid Saleem³, Samreen Zaidi⁴, Abdullah B Naveed⁵, Khalil Ahmad¹, Farah Naz Qamar¹

Affiliations

¹ Department of Pediatrics and Child Health, Aga Khan University, Stadium Road, Karachi, 74800, Pakistan.
² Department of Pediatrics, The Indus Hospital, Korangi Road, Karachi, Pakistan.
³ Children's Hospital and The Institute of Child Health, Multan, Pakistan.
⁴ National Institute of Blood Disease & Bone Marrow Transplantation, P.E.C.H.S, Karachi, Pakistan.
⁵ Medical College, Aga Khan University, Stadium Road, Karachi, 74800, Pakistan.

Abstract

Background: Primary Immunodeficiency Disorders (PIDs) are well-known disorders in the West. but the recognition and diagnosis of these disorders is challenging in developing countries. We present the spectrum of PIDs seen at a tertiary care center in Pakistan, identified using clinical case definitions and molecular methods.

Methods: A retrospective chart review of children suspected to have PID was conducted at the Aga Khan University Hospital (AKUH) Karachi, Pakistan from 2010 to 2016. Data on demographics, clinical features, family history of consanguinity, sibling death, details of laboratory workup done for PID and molecular tests targeted panel next generation sequencing (NGS) or whole exome sequencing (WES) performed at the Geha laboratory at Boston Children's Hospital, USA was collected. The study was exempted from the Ethical Review Committee of AKUH.

Results: A total of 43 children visited the hospital with suspected PID during the study period. Genetic testing was performed in 31/43 (72.1%) children. A confirmed diagnosis of PID was established in 20/43 (46.5%) children. A pathogenic gene variant was identified in 17(85%) of the 20 confirmed cases (Table 1). Twelve (60%) of the confirmed cases of PID were male. The most common presenting symptom was recurrent diarrhea 11/20 (55%). The mean (±S.D) age of the cases at the time of diagnosis was 4.2 (±4.1) years. Chronic granulomatous disease (CGD) was the most common 6/20 (30%) disorder, followed by severe combined immunodeficiency (SCID) 3/20 (15%), leukocyte adhesion deficiency (LAD) 3/20 (15%), agammaglobulinemia/hypogammaglobulinemia 3/20 (15%), and Hermansky-Pudlak Syndrome (HPS) 2/20 (10%). Wiskott-Aldrich Syndrome, Immunodeficiency Centromeric Instability and Facial Anomalies Syndrome (ICF 2), Trichohepatoenteric syndrome (TRES), and C3 deficiency were each diagnosed once {1/20 (4.3%) each} (Table 1). Of these 20 confirmed cases, almost all 19/20 (95%) had a family history of consanguinity. Sibling death was reported in 5/20 (25%) of these cases. Five out of the 20 (25%) children died over the 7-year period for various reasons.

Conclusion: PIDs are not uncommon in Pakistan; their diagnosis may be missed or delayed due to the overlapping of clinical features of PID with other diseases and a lack of diagnostic facilities. There is a need to build capacity for early recognition and diagnosis of PIDs to decrease morbidity and mortality.

Keywords: AFIP, Armed Forces Institute of Pathology; ARDS, Acute Respiratory Distress Syndrome; BCG, Bacille Calmette-Guerin; BMT, Bone Marrow Transplant; CGD, Chronic Granulomatous Disease; Children; Chronic granulomatous disease; Consanguineous marriages; DHR, Dihydrorhodamine; HPS, Hermansky-Pudlak Syndrome; I/V, Intravenous; ICF-2, Immunodeficiency Centromeric Instability and Facial Anomalies Syndrome; LAD, Leukocyte Adhesion Deficiency; LMIC, Low Middle Income Countries; NBT, Nitrotetrazolium blue test; NGS, Next-Generation Sequencing; OPV, Oral Polio Vaccine; PIDs, Primary Immunodeficiency Disorders; Primary immunodeficiency disorders; S/C, Subcutaneous; SCID, Severe Combined Immunodeficiency Disorder; TRES, Trichohepatoenteric syndrome; USA, United States of America; VDP, Vaccine Derived Poliovirus; WES, Whole Exome Sequencing.