Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency.
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.
Turul
Tuba
T
Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
Tezcan
Ilhan
I
Artac
Hasibe
H
de Bruin-Versteeg
Sandra
S
Barendregt
Barbara H
BH
Reisli
Ismail
I
Sanal
Ozden
O
van Dongen
Jacques J M
JJ
van der Burg
Mirjam
M
D017252:CD3 Complex / Q000235:genetics; D015704:CD4 Antigens / Q000235:genetics; D016827:CD8 Antigens / Q000235:genetics; D005183:Failure to Thrive; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D007223:Infant; D008231:Lymphopenia / Q000175:diagnosis / Q000453:epidemiology; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis / Q000235:genetics / Q000517:prevention & control; D015398:Signal Transduction / Q000502:physiology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000172:deficiency* / Q000235:genetics*
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human