Severe combined immunodeficiency (SCID) is an inherited diseases caused by the defective development of T- and/or B-lymphocytes refractory to common therapy. We report a 13-year old boy with combined immunodeficiency caused by a heterozygous mutation at cDNA position 1435 (c.1435C>T) in RAG1 gene. His father and grand-father carried the same heterozygous RAG1 gene mutation, and experienced anaphylactic rhinitis. His mother had mutations in 6 immunodeficiency-related heterozygous genes but no RAG1 mutation, and experienced thrombocytopenia. Both his parents had normal NK and T cell numbers, and serum immunoglobulin (Ig) levels. After birth, this patient had severe allergies to many food and drugs, and suffered from recurrent upper and lower respiratory tract infections every year. After admission, the patient complained of a generalized body rash with itches lasting about several years. We found severe granuloma lesions in the face, mouth and nose, lymphadenectasis and splenomegaly by physical examination (Figure 1a). Laboratory examinations demonstrated that he had a high eosinophilic granulocyte count as 2.19×109/L, but decreased NK cell numbers and CD4+/CD8+ T cell ratios, and IgG, IgM and IgA serum levels. This patient has been previously treated with immune-modulatory drugs including anti-histamine drugs, prednisone, γ-globulin, and chemotherapy including Cyclophosphamide, but lacking clinical improvement. In our center, after Methotrexate (1g/m2 q.w.)+L-asparaginase (10000 unit q.d.×10 days) + Dexamethasone (10mg/m2q.d.×5 days) chemotherapy, and immune enhancement therapy with γ-globulin(400mg/kg×5 days per month), the patient got his symptoms ameliorated (Figure 1b). Haploidentical hematopoietic stem cell transplantation (HCT) from his HLA 7/10 matched mother was subsequently applied, and the patient remained remission without HCT-related complications for at least 8 months after transplantation (Figure 1c). Our results thus showed the immune disorder in a boy caused by a novel heterozygous RAG1 gene c.1435C>T mutation which has been efficiently treated by our specific chemotherapy combined with HCT.

Figure 1
Figure 1.
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Disclosures

No relevant conflicts of interest to declare.

Topics:
boys, eosinophilia, granulomatous disorder, immunologic deficiency syndromes, mutation, rag1 gene, chemotherapy regimen, globulins, immunoglobulins, severe combined immunodeficiency

Author notes

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Asterisk with author names denotes non-ASH members.

© 2017 by The American Society of Hematology
2017
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