Introduction

Severe combined immunodeficiency (SCID) is the most serious inborn error of immunity, lethal if untreated. There are three SCID subtypes: typical (TS), atypical (AS) and Omenn syndrome (OS). The goal of this study is to characterize clinical and immunogenetic aspects of patients with different aforementioned types of SCID diagnosed in a single center and an attempt to select factors improving diagnosis in the areas without newborn screening.

Material and methods

This is a retrospective evaluation of the clinical course and hematological, biochemical, immunological and genetic tests leading to SCID diagnosis in 42 children.

Results

Median age of diagnosis was 4.4 months, higher for AS (8 months, p < 0.05). Median diagnostic delay (DD) was 2.5 months (4.7 months in AS children). Suspicion of the disease was raised by pediatricians (in 44.4% of all children), hematologists (19.4% of all children, 26.3% of AS children, with DD of 20 months), or dermatologists. The first symptoms were infections (64%), rash (22.2%), chronic diarrhea (5.6%), anemia (5.6%) and lymphopenia (2.8%). At the time of diagnosis, 79.5% of patients presented with lymphopenia. The median of recent thymic emigrants was 0.2%, 2.1%, 0.3% in TS, AS and OS, respectively. The most frequent pathogenic variants were found in the following genes: IL2RG (23.8%), RAG1/2 (16.6%), JAK3 (14.3%), ADA (11.9%) and IL7RA (4.8%). The overall survival rate was 69% in all children.

Conclusions

The diagnosis of SCID was established significantly later in the case of AS than TS and OS. The type of first symptoms does not differ between particular types of SCID. Lymphopenia is the most common symptom and the most often underestimated laboratory sign of SCID.