Zeta chain-associated protein kinase 70 (ZAP-70) deficiency is an exceptionally rare autosomal recessive form of T+B+NK+ combined immunodeficiency (CID), associated with a heterogeneous clinical and immunological phenotype. Due to the scarcity of reported cases, outcome data to guide therapeutic strategies, particularly hematopoietic stem cell transplantation (HSCT), are limited. Here, we describe the clinical, immunological, and genetic features, as well as transplantation outcomes and post-HSCT immune reconstitution, in thirteen novel patients managed at a single tertiary care center.
We retrospectively reviewed clinical, immunologic, genetic characteristics, HSCT outcome, and immune reconstitution for 13 patients who were diagnosed with ZAP-70 deficiency at King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
A total of thirteen patients were included, with a mean age at diagnosis of 4 months. The most common initial presentations were recurrent chest infections and skin abnormalities. Autoimmune manifestations and lymphoproliferation were also observed. Immunological evaluation revealed absent or severely reduced CD8+ T cell counts in most patients; however, two patients deviated from this pattern, demonstrating nearly normal CD8+ counts. Three ZAP-70 mutations in homozygous states were identified. Eleven patients underwent HSCT, with seven from fully matched sibling donors, three from mismatched related donor, and one from umbilical cord. Two patients required a second transplant for poor immune reconstitutions. At last follow-up, eight patients were alive with reasonable immune reconstitution.
Early recognition and timely HSCT are critical for improving outcomes in ZAP-70-deficient patients. Despite challenges in immune reconstitution, mixed lymphoid chimerism was sufficient to achieve clinical stability in the majority of patients.
