Atypical Omenn Syndrome due to Adenosine Deaminase Deficiency

We present here a novel case of an atypical Omenn syndrome (OS) phenotype due to mutations in the ADA gene encoding adenosine deaminase. This case is noteworthy for a significant increase in circulating CD56brightCD16- cytokine-producing NK cells after treatment with steroids for skin rash. 1. Introduction Omenn syndrome (OS) is a distinct manifestation of Severe Combined Immunodeficiency (SCID) characterized by erythroderma, hepatosplenomegaly, lymphadenopathy, eosinophilia, and elevated IgE and alopecia [1–3]. Patients with OS usually present in infancy with viral or fungal pneumonitis, chronic diarrhea, and failure to thrive, but in contrast to classic SCID patients also have the above-mentioned characteristics. Here we present a case of atypical OS in an infant with adenosine deaminase (ADA) deficiency. 2. Case Report A 2-month-old Somali boy, born to consanguineous parents, presented to our hospital with concerns for immunodeficiency. The initial symptoms included cough, diffuse skin rash (Figure 1), hepatosplenomegaly, and a sepsis-like syndrome. A complete sepsis workup was negative, except for an absolute lymphocyte count (ALC) of 0, which triggered evaluation for an underlying primary immunodeficiency. T-, B- and NK-cell quantitation in blood revealed a T-B-NK- phenotype consistent with Severe Combined Immunodeficiency (SCID). The molecular defect was likely thought to be in the ADA gene due to the ethnicity of the patient and the lymphocyte phenotype, therefore, ADA levels were tested and found to be 0 (reference range: 0.3–1.5/g Hb). Figure 1: Diffuse rash in an infant with ADA deficiency. Broad-spectrum antibiotics were initiated, but with negative cultures, were maintained on prophylactic antibiotics (Bactrim for Pneumocystis, initial Fluconazole followed by Caspofungin for antifungal, IVIG and Palivizumab for RSV). His skin rash was extensively evaluated and the pathology was initially regarded as possible graft versus host disease due to maternal engraftment [4], due to the presence of apoptotic keratinocytes. However, the absence of circulating T cells argued against that possibility and chimerism [5] studies on a skin biopsy revealed all cells to be XY in origin, confirming absence of maternal engraftment. Treatment was initiated with steroids and PEG-ADA (biweekly, 60？U/kg/week due to the absence of a matched donor for stem cell transplantation and unsuitability at the time for gene therapy [6]; trough plasma ADA levels were monitored while on PEG-ADA treatment-range of 30–40？mmol/hr/mL (target levels > 12？mmol/hr/mL), but shortly