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.
Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
Tuba
T
Turul
Ilhan
I
Tezcan
Hasibe
H
Artac
Sandra
S
de Bruin-Versteeg
Barbara H
BH
Barendregt
Ismail
I
Reisli
Ozden
O
Sanal
Jacques J M
JJ
van Dongen
Mirjam
M
van der Burg
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