ESPE Abstracts (2022) 95 RFC3.3

1Infectivology and Clinical Trials Research Department, Children's Hospital Bambino Gesù IRCCS, Rome, Italy; 2Endocrinology Unit, Children's Hospital Bambino Gesù IRCCS, Rome, Italy; 3Hepatology Gastroenterology and Nutrition Unit, Children's Hospital Bambino Gesù, Rome, Italy; 4Unit of Endocrinology and Rare Endocrine Diseases, Bari University, Bari, Italy; 5Pediatric Endocrinology Unit, Department of Mother and Child, University Hospital Federico II of Naples, Naples, Italy; 6Department of Human Pathology of Adulthood and Childhood, Messina University, Messina, Italy; 7S Raffaele Hospital IRCCS, Milan, Italy; 8Pediatric Endocrinology Unit, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy; 9Endocrine Unit, Department of Medicine, Padua University, Padua, Italy

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED, OMIM240300) is a rare monogenic disease due to biallelic mutations in the Autoimmune Regulator (AIRE) gene. This encodes for a thymus-enriched transcription factor responsible for central immune tolerance. Classic diagnostic criteria are the presence of two of main symptoms of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism (HP) and Addison’s disease (AD). Non-endocrine autoimmunity involving the liver, intestine, eye and kidney is generally reported in a minority of patients. In Finnish, Sardinian and Iranian Jew populations APECED develops at the highest prevalence with homozygous AIRE mutations c.769C>T, c.425C>T and c.254A>G having a founder effect respectively. American APECED patients showed enrichment of organ-specific non-endocrine manifestations starting early in life as compared to European cohorts. This observation led to revise diagnostic clinical criteria that would permit earlier diagnosis based on the appearance of one classic triad and one non-classical manifestation at young age in presence of IFNAbs or AIRE mutations (PMID29562162). We analysed the clinical, genetic and autoAbs profile in a series of 10 Italian APECED pediatric patients with gastrointestinal manifestations (5 males, 5 females). Seven patients presented APECED-associated hepatitis (APAH). In 3 patients this occurred as first disease manifestation; 2 patients developed APAH following HP; one following MC and one following the dyad CMC, HP. The mean age of APAH diagnosis was 7.9 years (range 1.5-13). APAH-related specificities LKMAbs tested positive in one patient, TPH in 3/7; AADC were enriched in 6/7 and cP450c21 in 5/7. Most frequent AIRE mutation was c.967_979del13. Six patients were affected by signs of constipation/diarrhea/malabsorption. One patient was also affected by iron-deficiency anemia and two by atrophic gastritis, of these one with pernicious anemia. The mean age of intestinal dysfunction diagnosis was 6.8 years (range 5.6-9). The sera of 4 patients tested positive for TPH Abs and of 4 for AADCAbs known to be associated with autoimmune enteropathy (AIE) in APECED. AIE-75 and villin Abs tested negative. All patients’ sera tested positive for IFNα4 and 9/10 for IFNωAbs. cP450c21Abs tested positive in 5/7 APAH patients and in 3/6 with gastrointestinal dysfunction. No specific AIRE genotype was prevalent. Based on the age of appearance of non-endocrine manifestations (29562162), Ferre-Lionakis criteria (27588307), similar to the American cohort, would have allowed an expedited clinical diagnosis in 8/10 patients. This emphasize the importance to evaluate non-endocrine manifestations such as APAH and gastrointestinal dysfunction for an earlier diagnosis of APECED even in European cohorts.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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