To gain insight into the peculiarities of clinical presentation and time of diagnosis in the population of patients with combined immunodeficiency treated in our center.

We retrospectively analyzed 22 patients with combined immunodeficiency treated in our center in the past 25 years. Clinical findings were collected, including age of presentation and age of diagnosis, genetic defects, consanguinity, family history, number and site of infections, presence of diarrhea, failure to thrive, skin rash, vaccine complications and type of treatment. Immunological findings included WBC with absolute counts, lymphocyte subsets and immunoglobulin levels.

Patients (n=22) with severe combined immunodeficiency (n=17) and other combined immunodeficiencies (n=5) were included in the study. Sixteen patients (77%) were male. The most common clinical manifestations were opportunistic infections. Most of the patients were diagnosed after 3 months of age. Prenatal diagnosis was performed in one patient (4.5%), two patients

(9%) did not undergo genetic analysis. The spectrum of genetic defect in our cohort show wide heterogeneity. Seventeen patients (77%) underwent HSCT, one patient (4.5%) is on enzyme replacement therapy. None of our patients have undergone gene therapy. Twelve patients (54.5%) died, of which four (18%) died before HSCT.

Combined immunodeficiencies are fatal without definitive therapy (HSCT or gene therapy). The outcomes are better if infants are diagnosed and treated in pre-symptomatic stage, preferably before 3.5 months of age. More and more countries are implementing newborn screening for primary immunodeficiency diseases in their health care systems to diagnose patients as early as possible and to prevent infections. For the same reason, we advocate for expanding our national neonatal screening program