![]() Some patients with DNA repair defects associated with SCID, such as Ligase-4 deficiency or Cernunnos/XLF may present with microcephalia and delayed neurological development. ![]() Patients with Adenosine-Deaminase (ADA)-deficiency may present with alveolar proteinosis ( 6) and/or bone abnormalities (cupping of osteochondral junctions) detectable on the chest radiograph. Specific Features Due to the Affected Gene A chronic swelling or ulceration at the BCG injection site or a chronic diarrhea after oral Rotavirus vaccination should lead to further diagnostic steps and the formal exclusion of a T-lymphocyte deficiency. Live vaccines with attenuated microorganisms, such as Bacille Calmette-Guérin (BCG) or Rotavirus, may lead to atypical infections and can have an unwanted diagnostic value. Cytomegalovirus (CMV) infection can be particularly severe and diffuse with pulmonary, liver, cardiac, intestinal, retinal, and/or central nervous system involvement. Intestinal infections with Rota-, Noro or Adenovirus can lead to severe chronic diarrhea. Airway infections due to viral ( Respiratory Syncytial Virus, Myxovirus, Adenovirus) and opportunistic microorganisms such as Pneumocystis jirovecii (PJP) can cause severe pneumonias requiring mechanical ventilation. Opportunistic infections can suggest a defect of specific cellular immunity but non-specific bacterial infections are also frequently observed in SCID patients ( 5). Patients are classically not infected at birth, but in the absence of diagnosis, they will eventually present with severe, atypical and/or recurrent life threatening infections. Some patients may also present with leaky-SCID, usually caused by hypomorphic mutations in classical SCID causing-genes, responsible for a less severe phenotype with infections and autoimmunity. In the absence of allogenic hematopoietic stem cell transplantation (HSCT) or gene therapy (GT), patients ultimately die generally within the first year of life. Some genetic defects cause non-immunological and disease specific features. Some patients may also present with signs of immune dysregulation caused by autologous (Omenn syndrome) or allogeneic (maternal GvHD) T cells. Usually, patients are asymptomatic at birth and present within their first weeks or months of life with infections and/or failure to thrive (FTT) ( 5). The clinical presentation of patients with SCID is variable. This immunophenotypic categorization does not replace molecular identification, which is key for prognosis ( 4). ![]() SCID entities are also classified by immunophenotype, depending on the presence of B-lymphocytes and NK cells, which are usually associated with specific gene defects (genotypes) ( Table 2).
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