Approaches to patients with variants in RAG genes: from diagnosis to timely treatment

Bulkhi, Adeeb; Dasso, Joseph F.; Schuetz, Catharina; Walter, Jolán E.

doi:10.1080/1744666x.2020.1670060

Cited by 8 publications

(6 citation statements)

References 84 publications

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“…It may present with IBD-like disease, autoimmune enteropathy, duodenitis, or severe noninfectious diarrhea. Detected infective agents are pneumocystis jirovecii, Candida species, and viral infections, such as cytomegalovirus (CMV) and adenovirus [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity in RAG1 and RAG2 deficiency: 35 cases from a single-centre

Karaatmaca,

Cagdas,

Esenboga

et al. 2024

Clinical and Experimental Immunology

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Recombination activating genes (RAG) 1/2 deficiency leads to combined T/B cell deficiency with varying clinical presentations. This study aimed to define the clinical/laboratory spectrum of RAG1/2 deficiency. We retrospectively reviewed the clinical/laboratory data of 35 patients, grouped them as severe combined immunodeficiency (SCID), Omenn Syndrome (OS), and delayed-onset combined immunodeficiency (CID) and reported nine novel mutations. Male/female ratio was 23/12. Median age of clinical manifestations was 1 months (mo) (0.5-2), 2 mo (1.25-5), and 14 mo (3.63-27), age at diagnosis was 4 mo (3-6), 4.5 mo (2.5-9.75), and 27 mo (14.5-70) in SCID (n=25;71.4%), OS (n=5;14.3%), and CID (n=5;14.3%) patients, respectively. Common clinical manifestations were recurrent sinopulmonary infections 82.9%, oral moniliasis 62.9%, diarrhea 51.4%, and eczema/dermatitis 42.9%. Autoimmune features were present in 31.4% of the patients; 80% was in CID patients. Lymphopenia was present in 92% of SCID, 80% of OS, and 80% of CID patients. All SCID and CID patients had low T (CD3, CD4, and CD8), low B, and increased NK cell numbers. Twenty-eight patients underwent hematopoietic stem cell transplantation (HSCT), whereas seven patients died before HSCT. Median age at HSCT was 7 months (4-13,5). Survival differed in groups; maximum in SCID patients who had an HLA-matched family donor, minimum in OS. Totally 19 (54.3%) patients survived. Early molecular genetic studies will give both individualized therapy options, and a survival advantage because of timely diagnosis and treatment. Further improvement in therapeutic outcomes will be possible if clinicians gain time for HSCT.

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Section: Discussionmentioning

confidence: 99%

Heterogeneity in RAG1 and RAG2 deficiency: 35 cases from a single-centre

Karaatmaca,

Cagdas,

Esenboga

et al. 2024

Clinical and Experimental Immunology

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“…RAG genes are also highly polymorphic; therefore, all novel variants require confirmation of pathogenicity. This can be done through BCR or TCR repertoire studies and/or in vitro recombination assays (17,26,27).…”

Section: Discussionmentioning

confidence: 99%

Asymptomatic Infant With Atypical SCID and Novel Hypomorphic RAG Variant Identified by Newborn Screening: A Diagnostic and Treatment Dilemma

et al. 2020

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“…Three disorders are discussed here in more detail, as follows: 1) null mutations in recombinase activating gene 1 or gene 2 (RAG 1 or RAG 2). These mutations cause SCID; however, hypomorphic mutations with residual RAG activity can lead to a PCID classified as atypical SCID [26][27][28]. Systemic granulomatous inflammation is a hallmark of the disorder.…”

Section: Combined Immunodeficienciesmentioning

confidence: 99%

“…Symptoms of mild RAG deficiency can be controlled by immunosuppression but long-term remission cannot be achieved in all patients. Some cases of partial RAG deficiency, especially atypical SCID, can only be cured with SCT [27,28]. The diverse phenotype of (P)CIDs and the individual clinical course has therefore to be taken into account to decide whether SCT might be a viable option for affected patients [26,27].…”

Section: Combined Immunodeficienciesmentioning

confidence: 99%

Pulmonary granulomatosis of genetic origin

et al. 2021

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Granulomatous inflammation of the lung can be a manifestation of different conditions and can be caused by endogenous inflammation or external triggers. A multitude of different genetic mutations can either predispose patients to infections with granuloma-forming pathogens or cause autoinflammatory disorders, both leading to the phenotype of pulmonary granulomatosis. Based on a detailed patient history, physical examination and a diagnostic approach including laboratory workup, pulmonary function tests (PFTs), computed tomography (CT) scans, bronchoscopy with bronchoalveolar lavage (BAL), lung biopsies and specialised microbiological and immunological diagnostics, a correct diagnosis of an underlying cause of pulmonary granulomatosis of genetic origin can be made and appropriate therapy can be initiated. Depending on the underlying disorder, treatment approaches can include antimicrobial therapy, immunosuppression and even haematopoietic stem cell transplantation (HSCT). Patients with immunodeficiencies and autoinflammatory conditions are at the highest risk of developing pulmonary granulomatosis of genetic origin. Here we provide a review on these disorders and discuss pathogenesis, clinical presentation, diagnostic approach and treatment.

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Approaches to patients with variants in RAG genes: from diagnosis to timely treatment

Cited by 8 publications

References 84 publications

Heterogeneity in RAG1 and RAG2 deficiency: 35 cases from a single-centre

Heterogeneity in RAG1 and RAG2 deficiency: 35 cases from a single-centre

Asymptomatic Infant With Atypical SCID and Novel Hypomorphic RAG Variant Identified by Newborn Screening: A Diagnostic and Treatment Dilemma

Pulmonary granulomatosis of genetic origin

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