Clinical, Laboratory, and Molecular Findings for 63 Patients With Severe Combined Immunodeficiency: A Decade's Experience

Fazlollahi, Mohammad Reza; Pourpak, Zahra; Hamidieh, Amir Ali; Movahedi, Masoud; Houshmand, Massoud; Badalzadeh, Mohsen; Nourizadeh, Mohammad; Mahloujirad, Maryam; Arshi, Saba; Nabavi, Mohammad; Gharagozlou, Mohammad; Khayatzadeh, Alireza; Dabbaghzade, Abbas; Atarod, Lida; Zandieh, Fariborz; M, Sadeghi Shabestary; Mesdaghi, Mehrnaz; Mohammadzadeh, Iraj; Mahdaviani, Seyed Alireza; Eslamian, Mohammad Hossein; Pesaran, F; Bahraminia, Emad; Abolnezhadian, Farhad; Arij, Z; Moin, Mostafa

doi:10.18176/jiaci.0147

Cited by 22 publications

(7 citation statements)

References 15 publications

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“…Ninety-one percent of our cohort were a product of consanguineous marriage. This is even greater than reported in large SCID cohorts from Iran (87.3%), KSA (60%) and India (36%) ( 8 , 20 , 21 ). Remarkably, in our cohort, 66% of affected children had a positive family history of SCID for which half of them (33%) reported a sibling death, much higher than what have been reported in Italy (5.6%) and Iran (3%) ( 20 , 22 ).…”

Section: Discussionmentioning

confidence: 55%

A Decade Experience on Severe Combined Immunodeficiency Phenotype in Oman, Bridging to Newborn Screening

et al. 2021

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IntroductionSevere combined immunodeficiency (SCID) results from various monogenic defects that impair immune function and brings on early severe and life-threatening infections. The main stay of treatment for SCID is hematopoietic stem cell transplant (HSCT) with near normal survival at 5 years for an early transplant done at or before the age of 3.5 months of life and the patient is maintained free of infections. Although overall rare, it constitutes a major burden on affected children, their families and on the health system especially in communities with a high rate of consanguinity where incidence and prevalence of recessive inborn errors of immunity (IEI) are expected to be high.MethodHere, we report the clinical, immunological, and molecular findings in 36 children diagnosed with SCID from a single tertiary center in Oman for the last decade.ResultsWe observed a median annual incidence rate of 4.5 per 100,000 Omani live births, and 91.7% of affected children were born to consanguineous parents. Twenty-three children (63.9%) fulfilled the criteria for typical SCID. The median age at onset, diagnosis and diagnostic delay were 54, 135, and 68 days, respectively. The most common clinical manifestations were pneumonia, septicemia, and chronic diarrhea. Eleven children (30.6%) have received hematopoietic stem cell transplant (HSCT) with a survival rate of 73%. The most frequent genetic cause of SCID in this cohort (n = 36) was (RAG-1), encoding for recombination activating gene (n = 5, 13.9%). Similarly, Major histocompatibility complex type II deficiency accounted for (n = 5, 13.9%) of our cohort.ConclusionOur report broadens the knowledge of clinical and molecular manifestations in children with SCID in the region and highlights the need to initiate newborn based screening program (NBS) program.

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Section: Discussionmentioning

confidence: 55%

A Decade Experience on Severe Combined Immunodeficiency Phenotype in Oman, Bridging to Newborn Screening

et al. 2021

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“…Majority of our cases belonged to the category of T − B − SCID (39%) followed by T − B + SCID (28%). In Greece, 40% SCID patients belonged to T − B − NK + category and in Serbia and Montenegro, 57% patients with SCID and Omenn syndrome presented with T − B − NK + SCID phenotype (26). In the registry of Saudi Arabia for combined immunodeficiencies, T − B − was the most common type; 17% followed by T − B + found in 5% and Omenn syndrome in 3.6% (26).…”

Section: Discussionmentioning

confidence: 99%

“…In Greece, 40% SCID patients belonged to T − B − NK + category and in Serbia and Montenegro, 57% patients with SCID and Omenn syndrome presented with T − B − NK + SCID phenotype (26). In the registry of Saudi Arabia for combined immunodeficiencies, T − B − was the most common type; 17% followed by T − B + found in 5% and Omenn syndrome in 3.6% (26). China's SCID registry has reported 66.7% of patients with B + SCID and 7.1% of the cohort with B − SCID (25).…”

Section: Discussionmentioning

confidence: 99%

Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India

et al. 2019

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Severe combined immunodeficiency (SCID) represents one of the most severe forms of primary immunodeficiency (PID) disorders characterized by impaired cellular and humoral immune responses. Here, we report the clinical, immunological, and molecular findings in 57 patients diagnosed with SCID from India. Majority of our patients (89%) presented within 6 months of age. The most common clinical manifestations observed were recurrent pneumonia (66%), failure to thrive (60%), chronic diarrhea (35%), gastrointestinal infection (21%), and oral candidiasis (21%). Hematopoietic Stem Cell Transplantation (HSCT) is the only curative therapy available for treating these patients. Four patients underwent HSCT in our cohort but had a poor survival outcome. Lymphopenia (absolute lymphocyte counts/μL <2,500) was noted in 63% of the patients. Based on immunophenotypic pattern, majority of the cases were T−B− SCID (39%) followed by T−B+ SCID (28%). MHC class II deficiency accounted for 10.5% of our patient group. A total of 49 patients were molecularly characterized in this study and 32 novel variants were identified in our cohort. The spectrum of genetic defects in our cohort revealed a wide genetic heterogeneity with the major genetic cause being RAG1/2 gene defect (n = 12) followed by IL2RG (n = 9) and JAK3 defects (n = 9). Rare forms of SCID like Purine nucleoside phosphorylase (PNP) deficiency, reticular dysgenesis, DNA-Protein Kinase (DNA-PKcs) deficiency, six cases of MHC class II deficiency and two ZAP70 deficiency were also identified in our cohort. Fourteen percent of the defects still remained uncharacterized despite the application of next generation sequencing. With the exception of MHC class II deficiency and ZAP70 deficiency, all SCID patients had extremely low T cell receptor excision (TRECs) (<18 copies/μL).

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“…15,27 Unfortunately, BCG vaccination was carried out in 21 out of our 33 SCID patients (64%) which resulted incomplicated problems in 5 patients. 28 To avoid the postvaccination complications and also timely finding of appropriate donors, it is highly recommended to run a national screening program to identify suspected patients especially in families without a positive history of PIDs.…”

Section: T a B L Ementioning

confidence: 99%

Newborn screening using TREC/KREC assay for severe T and B cell lymphopenia in Iran

et al. 2018

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T-cell receptor excision circles (TRECs) and κ-deleting recombination excision circles (KRECs) are recently used for detection of T or B cell lymphopenia in neonates based on region-specific cutoff levels. Here, we report cutoffs for TREC and KREC copies useful for newborn screening and/or diagnosis of primary immunodeficiency diseases (PID) in Iran. DNA was extracted from a single 3.2 mm punch of dried blood spots collected from 2160 anonymized newborns referred to two major referral health centers between 2014 and 2016. For refinement of the cutoffs, 51 patients with a definite diagnosis of severe combined immunodeficiency, X-linked agammaglobulinaemia and combined immunodeficiency, including ataxia telangiectasia, human phosphoglucomutase 3 and Janus kinase-3 deficiency, as well as 47 healthy controls were included. Samples from patients with an X-linked hyper-IgM-syndrome, Wiskott-Aldrich syndrome and DNA ligase 4 deficiency were considered as disease controls. Triplex-quantitative real-time PCR was used. Cutoffs were calculated as TRECs < 11 and KRECs < 6 copies with an ACTB > 700 copies with sensitivity of 100% for TREC and 97% for KREC. Among thirty anonymized newborn samples (1.5%) with abnormal results for TREC and/or KREC, only twenty one available cases were retested and shown to be in the normal range except for three samples (0.15%). All of the patients with a definitive diagnosis were correctly identified based on our established TREC/KREC copy numbers. Determining cutoffs for TREC/KREC is essential for correctly identifying children with PID in newborn screening. Early diagnosis of PID patients enables appropriate measures and therapies like stem cell transplantation. This article is protected by copyright. All rights reserved.

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Clinical, Laboratory, and Molecular Findings for 63 Patients With Severe Combined Immunodeficiency: A Decade's Experience

Cited by 22 publications

References 15 publications

A Decade Experience on Severe Combined Immunodeficiency Phenotype in Oman, Bridging to Newborn Screening

A Decade Experience on Severe Combined Immunodeficiency Phenotype in Oman, Bridging to Newborn Screening

Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India

Newborn screening using TREC/KREC assay for severe T and B cell lymphopenia in Iran

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