Removal of Immunosuppression Unmasks a Case of Autoimmune Lymphoproliferative Syndrome (ALPS)

Abstract

RATIONALE: DiGeorge syndrome (DGS) is the result of microdeletions of chromosome 22q11.2, resulting in a highly variable phenotype. Since limited clinical information is available, the purpose of this study was to characterize the immunologic status of a cohort of Hispanic DGS patients. METHODS: We studied 50 Hispanic patients diagnosed with DGS (64% confirmed using FISH), ages 0-21 years old (27 females and 23 males, mean age of diagnosis 4.1 6 2.1 years) by retrospective medical record review. Immune studies including lymphocyte subsets, mitogen proliferation, serum immunoglobulins and specific antibody response, and other clinical data were recorded. RESULTS: Nine patients (18%) had normal Tand B lymphocyte numbers, and normal total serum immunoglobulins. Twenty six patients (52%) had decreased T cells (both CD4+ and CD8+). Both T and B lymphocytes were affected in five (10%) patients. Five patients (10%) had decreased vaccine titers, two patients (4%) had hypogammaglobulinemia, and two patients (4%) had reduced, but not absent, proliferative response to mitogens. No patients had complete DGS. A variety of pre-diagnosis infections were found in 20% of patients. Post-diagnosis infections were present in 52%, the majority Otitis Media (28%). Prophylactic antibiotics were given to 20% of the patients. Cardiac malformations were common (82%). Other affected systems included: endocrine (48%), gastrointestinal (54%), and neurologic (56%). Developmental disorders included speech delay (78%) and learning disabilities (54%). CONCLUSIONS: Hispanic patients with partial DGS had diminished T lymphocyte numbers and hypogammaglobulinemia, similar to those previously described in the literature.