One of the severe combined immunodeficiencies (SCIDs), which is caused by a genetic defect in the signal transduction pathways involved in T-cell activation, is the ZAP70 deficiency. Mutations in ZAP70 lead to both abnormal thymic development and defective T-cell receptor (TCR) signaling of peripheral T-cells. In contrast to the lymphopenia in most SCID patients, ZAP70-deficient patients have lymphocytosis, despite the selective absence of CD8+ T-cells. The clinical presentation is usually before 2 years of age with typical findings of SCID. Here, we present three new ZAP70-deficient patients who vary in their clinical presentation. One of the ZAP70-deficient patients presented as a classical SCID, the second patient presented as a healthy looking wheezy infant, whereas the third patient came to clinical attention for the eczematous skin lesions simulating atopic dermatitis with eosinophilia and elevated immunoglobulin E (IgE), similar to the Omenn syndrome. This study illustrates that awareness of the clinical heterogeneity of ZAP70 deficiency is of utmost importance for making a fast and accurate diagnosis, which will contribute to the improvement of the adequate treatment of this severe immunodeficiency.

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Keywords T-cell receptor signaling, T-cells, ZAP70, severe combined immunodeficiency
Persistent URL dx.doi.org/10.1007/s00431-008-0718-x, hdl.handle.net/1765/15493
Citation
Turul, T, Tezcan, I, de Bruin-Versteeg, S, Barendregt, B.H, Reisli, I, Sanal, O, … van der Burg, M. (2009). Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency. European Journal of Pediatrics, 168(1), 87–93. doi:10.1007/s00431-008-0718-x