Novel Pathogenic Variants of the AIRE Gene in Two Autoimmune Polyendocrine Syndrome Type I Cases with Atypical Presentation: Role of the NGS in Diagnostic Pathway and Review of the Literature.

Background. Autoimmune polyglandular syndrome type 1 (APS-1) with or without reversible metaphyseal dysplasia is a rare genetic disorder due to inactivating variants of the autoimmune regulator, AIRE, gene. Clinical variability of APS-1 relates to pleiotropy, and the general dysfunction of self-tolerance to organ-specific antigens and autoimmune reactions towards peripheral tissues caused by the underlying molecular defect. Thus, early recognition of the syndrome is often delayed, mostly in cases with atypical presentation, and the molecular confirm through the genetic analysis of the AIRE gene might be of great benefit. Methods. Our methods were to investigate, with a multigene panel next generation sequencing approach, two clinical cases, both presenting with idiopathic hypoparathyroidism, also comprising the AIRE gene; as well as to comment our findings as part of a more extensive review of literature data. Results. In the first clinical case, two compound heterozygote pathogenic variants of the AIRE gene were identified, thus indicating an autosomal recessive inheritance of the disease. In the second case, only one AIRE gene variant was found and an atypical dominant negative form of APS-1 suggested, later confirmed by further medical ascertainments. Conclusions. APS-1 might present with variable and sometimes monosymptomatic presentations and, if not recognized, might associate with severe complications. In this context, next generation diagnostics focused on a set of genes causative of partially overlapping disorders may allow early diagnosis.

Stories of experiences of care for growth hormone deficiency: the CRESCERE project.

AIMS: Growth hormone deficiency therapy is demanding for patients and caregivers. Teams engaged in the clinical management of growth hormone deficiency therapy need to know how families live with this condition, to provide an adequate support and prevent the risk of withdrawal from therapy. METHODS: Using Narrative Medicine, testimonies from patients, their parents and providers of care were collected from 11 Italian centers. Narrations were analyzed throughout an elaboration of recurring words and expressions. RESULTS: Although care management and outcomes were considered satisfying in the 182 collected narratives, recurring signals of intolerance among adolescents and the worry of not being well informed about side effects among parents are open issues. CONCLUSION: Narratives found that communication issues could decrease adherence and influence the physicians' clinical practice.