ORIGINAL RESEARCH Severe Combined Immunodeficiency in Serbia and Montenegro Between Years 1986 and 2010: A Single-Center Experience Srdjan Pasic & Dragana Vujic & Dobrila Veljković & Bojana Slavkovic & Marija Mostarica-Stojkovic & Predrag Minic & Aleksandra Minic & Goran Ristic & Silvia Giliani & Anna Villa & Cristina Sobacchi & Desa Lilić & Mario Abinun Received: 9 September 2013 /Accepted: 20 January 2014 /Published online: 1 February 2014 # Springer Science+Business Media New York 2014 Abstract Severe combined immunodeficiency (SCID), in- cluding the ‘variant’ Omenn syndrome (OS), represent a heterogeneous group of monogenic disorders characterized by defect in differentiation of T- and/or B lymphocytes and susceptibility to infections since birth. In the period of 25 years, between January 1986 and December 2010, a total of 21 patients (15 SCID, 6 OS) were diagnosed in Mother & Child Health Institute of Serbia, a tertiary-care teaching University hospital and a national referral center for patients affected with primary immunodeficiency (PID). The diagno- ses were based on anamnestic data, clinical findings, and immunological and genetic analysis. The median age at the onset of the first infection was the 2nd month of life. Seven (33 %) patients had positive family history for SCID. Out of five male infants with T-B+NK- SCID phenotype, mutation analysis revealed interleukin-2 (common) gamma-chain re- ceptor (IL2RG) mutations in 3 with positive X-linked family history, and Janus-kinase (JAK)-3 gene defects in the other two. Six patients had T-B-NK+ SCID phenotype and further 6 features of OS, 11 of which had recombinase-activating gene (RAG1or RAG2) and 1 Artemis gene mutations. One child with T+B+NK+ SCID phenotype as well had proven RAG mutation. One child each with T-B+NK+ SCID phenotype, CD8 lymphopenia and unknown phenotype remained without known underlying genetic defect. Of the eight patients who underwent hematopoetic stem cell transplant (HSCT) 5 sur- vived, the other 13 died between 2 days and 12 months after diagnosis was made. Early diagnosis of SCID, before onset of severe infections, offers possibility for HSCT and cure. Education of primary-care pediatricians, in particular includ- ing awareness of the risk of using live vaccines and non- irradiated blood products, should improve prognosis of SCID in our setting. Keywords Severe combined immunodeficiency . Omenn syndrome . RAG deficiency Introduction Severe combined immunodeficiency (SCID), including the Omenn syndrome (OS), represents a group of rare, monogenic diseases with profound defect of T and/or B cell differentiation [1–4]. We undertook a retrospective study with aim to inves- tigate clinical characteristics, molecular diagnosis and out- come in infants who were diagnosed with SCID or OS in Serbia and Montenegro in the period of 25 years, between January 1986 to December 2010. S. Pasic : D. Vujic : D. Veljković : B. Slavkovic : P. Minic : A. Minic : G. Ristic Pediatric Clinic, Mother & Child Health Institute “Dr Vukan Čupić”, Belgrade, Serbia M. Mostarica-Stojkovic Institute for Microbiology and Immunology, Medical Faculty, University of Belgrade, Belgrade, Serbia S. Giliani Clinica Pediatrica, Spedali Civili, Brescia, Italy A. Villa : C. Sobacchi Istituto per Technologie Biologiche Avanzzate, Segrate, Milan, Italy D. Lilić Institute of Cellular Medicine, Medical School, University of Newcastle, Newcastle upon Tyne, UK M. Abinun Department of Paediatric Immunology, Great North Children’ s Hospital, Newcastle upon Tyne, UK S. Pasic (*) Mother and Child Health Institute, Medical Faculty, University of Belgrade, Radoja Dakića 8, 11070 Belgrade, Serbia e-mail: pasics@ikomline.net J Clin Immunol (2014) 34:304–308 DOI 10.1007/s10875-014-9991-9