ESPE2024 Poster Category 2 Late Breaking (107 abstracts)
Clinical and molecular characteristics of 26 patients with P450 oxidoreductase deficiency: A multicenter study
Melek Yildiz 1 , Ozge Bayrak Demirel 1 , Atilla Cayir 2 , Edip Unal 3 , Ayca Dilruba Aslanger 4 , Sare Betul Kaygusuz 5,6 , Ahmet Kahveci 7 , Teoman Akcay 8 , Ihsan Turan 9 , Korcan Demir 10 , Ruken Yildirim 11 , Zumrut Kocabey Sutcu 12 , Emrullah Arslan 13 , Esra Deniz Papatya Cakir 14 , Leyla Akin 15 , Seniha Kiremitci Yilmaz 16 , Tulay Guran 7 & Firdevs Bas 1
1Istanbul University, Istanbul Faculty of Medicine, Department of Pediatric Endocrinology, Istanbul, Turkey. 2Erzurum City Hospital, Erzurum, Turkey. 3Dicle University Faculty of Medicine, Department of Pediatric Endocrinology, Diyarbakir, Turkey. 4Istanbul University, Istanbul Faculty of Medicine, Department of Medical Genetics, Istanbul, Turkey. 5Istanbul Medeniyet University, School of Medicine, Department of Pediatric Endocrinology, Istanbul, Turkey. 6Istanbul University, Institute of Health Sciences, Department of Genetics, Istanbul, Turkey. 7Marmara University Faculty of Medicine, Department of Pediatric Endocrinology, Istanbul, Turkey. 8Uskudar University Medical Faculty, Department of Pediatrics, Sisli Memorial Hospital Pediatric Endocrinology, Istanbul, Turkey. 9Cukurova University Faculty of Medicine, Department of Pediatric Endocrinology, Adana, Turkey. 10Dokuz Eylul University, Division of Pediatric Endocrinology, Izmir, Turkey. 11Diyarbakir Children’s Hospital, Diyarbakir, Turkey. 12Basaksehir Cam and Sakura City Hospital, Pediatric Endocrinology, Istanbul, Turkey. 13Ege University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, Izmir, Turkey. 14University of Health Sciences, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Clinic of Pediatric Endocrinology, Istanbul, Turkey. 15Ondokuz Mayis University Faculty of Medicine, Department of Pediatric Endocrinology, Samsun, Turkey. 16University of Health Sciences, Haseki Training and Research Hospital, Pediatric Endocrinology, Istanbul, Turkey
Background: P450 oxidoreductase (POR) deficiency is a rare cause of congenital adrenal hyperplasia (CAH) with a wide spectrum of clinical phenotypes including glucocorticoid deficiency, difference/disorder of sex development (DSD), skeletal malformations, and Antley-Bixler syndrome. We describe the clinical and molecular characteristics of a large cohort with POR deficiency with long-term data.
Methods: The medical records of patients diagnosed with POR deficiency at 14 different pediatric endocrinology centers were retrospectively reviewed for their demographic, clinical, and laboratory characteristics.
Results: A total of 26 patients (7 females) from 23 unrelated families were included in the study. One patient was raised in the opposite sex to its karyotype. The median age at the last follow-up was 11.5 (range 0.5-23.5) years, with a median age at presentation of 1.3 (range 0-16.4) years. The birth weight SDS was -0.8 ± 0.9; with 3 cases of SGA. The maternal virilization rate was 23%, and the consanguinity rate was 73%. DSD affected 69% of the patients. Among males, the cryptorchidism rate was 74%. Presence of craniosynostosis, Antley-Bixler phenotype, limb contractures, and neurocognitive impairment were 27%, 50%, 50%, and 27%, respectively. Adrenal insufficiency and glucocorticoid usage were present in 84.6% of cases, with an average dose of 11.6 ± 2.3 mg/m2/day. The rate of genital corrective surgery was 48%. Genetic analysis of POR gene revealed 14 novel variants (c.1257C>A, p.Pro399_Gln401dup, c.929_937delTCTCGGACT, p.Met533Thr, p.L374H, c.238-1G>A, p.Pro399_Gln401del, c.1197_1198insTCGGAGCCC, p.R457H, p.Tyr607Cys, p.Asn637Glyfs, p.Asn82Ile, p.Pro399_Glu401del, c.694-695+2del). p.R457H was the most frequent variant (9/42, 21.4%). Six of the 21 genetically proven index cases had compound heterozygous variants (28.6%), while all others were homozygous.
Conclusion: The relative prevalence of POR deficiency is not known but might be higher particularly in populations with high rates of consanguinity. The results will enhance the understanding and knowledge of pediatric endocrinologists regarding POR deficiency and provide valuable insights into management of the disease. In our study, the variant spectrum was broad, and numerous new variants were identified. Performing a comprehensive molecular analysis for patients with suspected POR deficiency seems to be reasonable.
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