Recombinase Activating Gene 1 Deficiencies Without Omenn Syndrome May Also Present With Eosinophilia and Bone Marrow Fibrosis

Abstract

Background: Severe combined immunodeficiency (SCID) syndromes are a heterogenous group of diseases characterized by impairment in both cellular and humoral immunity with a range of genetic disorders. Complete recombinase activating gene (RAG) deficiency is associated with classical T^-B^-NK⁺ SCID which is the most common phenotype of Turkish SCID patients. There is a broad spectrum of hypomorfic RAG mutations including Omenn syndrome, leaky or atypical SCID with expansion of gamma delta T cells, autoimmunity and cytomegalovirus (CMV) infections.

Methods: Twenty-one (44%) patients had RAG1 deficiency of all 44 SCID patients followed up by pediatric immunology department. A retrospective analysis was conducted on the medical records of all SCID patients with RAG1 deficiency.

Results: Eight patients were classified as T^-B^-NK⁺ SCID, five patients as T⁺B^-NK⁺ SCID (three of these were Omenn phenotype), and eight patients as T⁺B⁺NK⁺ SCID phenotype. Mean age of the whole study group, mean age at onset of symptoms and mean age at diagnosis were 87.7 73.8 (12 - 256), 4.4 8.2 (1 - 36) and 29.1 56.8 (1 - 244) months, respectively. Consanguinity was present in 11 (52%) of 21 patients. Autoimmunity was found in six patients (28%). Ten patients (47%) had CMV infection, four (19%) had Epstein-Barr virus (EBV) infections and three (14%) had Bacillus Calmette-Guerin (BCG) infections. Seven patients who had refractory cytopenia (two pancytopenia and five bicytopenia) underwent bone marrow biopsy, three of whom had bone marrow fibrosis. Future evaluations must be considered about bone marrow fibrosis in RAG1 deficiency patients. Eosinophilia was observed in 10 patients, seven of whom did not have Omenn phenotype.

Conclusion: Non-Omenn phenotype RAG1 deficiencies can also present with eosinophilia. This report is presented to emphasize that RAG1 mutations may lead to diverse clinical phenotypes.




J Clin Med Res. 2016;8(5):379-384
doi: http://dx.doi.org/10.14740/jocmr2316w