ECE2024 Eposter Presentations Adrenal and Cardiovascular Endocrinology (155 abstracts)
Polygenic risk score for autoimmune Addison’s disease combined with whole-genome sequencing identifies patients with undiagnosed monogenic primary adrenal insufficiency
Maribel Aranda-Guillen 1 , Ileana R. Botusan 1,2 , Venuja Fernando 1 , Ellen Røyrvik 3,4,5 , Anette Susanne Bøe Wolff 3,4,6 , Stefan Johansson 3,7 , Eystein Sverre Husebye 1,3,4,6 , Sophie Bensing 2,8 , Olle Kämpe 1,2 & Daniel Eriksson 1,9
1Karolinska Institutet, Center for Molecular Medicine, Department of Medicine, Solna, Stockholm, Sweden; 2Karolinska University Hospital, Department of Endocrinology, Stockholm, Sweden; 3University of Bergen, Department of Clinical Science, Bergen, Norway; 4K.G. Jebsen Center for Autoimmune Disorders, Bergen, Norway; 5Norwegian Institute of Public Health, Department of Genetics and Bioinformatics, Bergen, Norway; 6Haukeland University Hospital, Department of Medicine, Bergen, Norway; 7Haukeland University Hospital, Department of Medical Genetics, Bergen, Norway; 8Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden; 9Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala, Sweden
Background: Primary adrenal insufficiency (PAI) is sometimes misdiagnosed as autoimmune Addison’s disease (AAD), affecting clinical management and genetic counselling. We tested a polygenic risk score (PRS) for AAD (PRS14AAD) as a tool to reevaluate disease etiology and identify patients misdiagnosed with AAD.
Methods: We calculated the PRS14AAD in a cohort of patients diagnosed with AAD but lacking 21-hydroxylase autoantibodies (n=124). Patients with low genetic susceptibility to AAD were selected for whole-genome sequencing to detect potential monogenic causes (n=35).
Results: Among the 35 patients, monogenic PAI was found in 5 (14%) and suspected in 3 additional cases (9%). Three out of the 5 rediagnosed patients developed the disease in adulthood, indicating late-onset monogenic disease associated with hypomorphic genetic variants.
Conclusion: A PRS for AAD can help identify potential monogenic cases, regardless of the age at diagnosis. Early identification of the underlying cause of PAI enables accurate management and correct genetic counselling
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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