Severe combined immunodeficiency with a homozygous c.464T>C (p.Leu155Pro) mutation in the RAG2 gene in a country without neonatal screening: Report of two clinical cases

Abstract

Introduction: Severe combined immunodeficiency (SCID) is a disorder belonging to the broad spectrum of inborn errors of immunity (IEI), characterized by a predisposition to develop recurrent, severe, difficult-to-treat opportunistic infections. This disorder is associated with abnormalities in genes of the adaptive immune system and should be suspected in patients with infections during the first months of life, mainly due to fungal pathogens and intracellular agents. Case Presentation: Two cases of SCID diagnosed at the General Hospital with Specialties "Juan María de Salvatierra” in Baja California Sur (BCS), México in 2022 are described. The first patient presented persistent candidiasis stomatitis with no response to oral treatment. The second patient presented mycotic dermatitis and oropharyngeal candidiasis compatible with Candida albicans and multiple episodes of multi-treated airway infection with partial remission. The diagnosis was completed with a genetic panel that showed a mutation in RAG2 homozygous variant c.464T>C (p.Leu155Pro) in both patients. Conclusions: SCID should be considered in patients with recurrent and difficult-to-treat infectious diseases in the first months of life. For its timely detection, implementing neonatal screening quantifying of T-cell receptor excision circles (TRECs) is recommended. This method is not available in Mexico, so it has been relevant to have physicians trained in the timely clinical identification of the disease. Thanks to the prompt referral of both patients to our hospital, we could treat the comorbidities associated with SCID, provide a specific molecular diagnosis, and transfer the patients to a hospital specialized in bone marrow transplantation for definitive treatment.