ESPE2022 Rapid Free Communications Late Breaking (6 abstracts)
Genotype, phenotype characteristics and long-term follow-up of patients with Vitamin D Dependent Rickets Type IA (VDDR1a): A nationwide multicentre retrospective cross-sectional study
Atilla Cayir 1 , Huseyin Demirbilek 2 , Ayberk Turkyılmaz 3 , Serap Turan 4 , Abdullah Bereket 4 , Feyza Darendeliler 5 , Mehmet Nuri Özbek 6 , Edip Ünal 7 , Deniz Okdemir 8 , Ihsan Esen 8 , Erdal Eren 9 , Ruken Yıldırım 10 , Semra Çetinkaya 11 , Kadriye Cansu Sahin 9 , Ahmet Anık 12 , Ayşe Sena Dönmez 1 , Ayşe Pınar Öztürk 5 , Elvan Bayramoğlu 11 , Muammer Buyukinan 13 , Fatih Gurbuz 14,15 , Korcan Demir 16 , Suna Kılınç 17 , Sare Betul Kaygusuz 4 , Gamze Çelmeli 12 , Beray Selvi Eklioglu 18 , Sezer Acar 19 , Fatma Dursun 20 , Ihsan Turan 21 , Beyhan Özkaya 19 , Erdal Kurnaz 11 , Rıza Taner Baran 22 & Behzat Özkan 19
1Department of Paediatric Endocrinology, Erzurum Training and Research Hospital, Erzurum, Turkey; 2Department of Paediatric Endocrinology, Hacettepe University Faculty of Medicine, Ankara, Turkey; 3Department of Medical Genetics, Karadeniz Technical University Faculty of Medicine, Department of Medical Genetics, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey; 4Department of Pediatric Endocrinology, Marmara University School of Medicine, Istanbul, Turkey; 5Istanbul Faculty of Medicine, Department of Pediatrics, Pediatric Endocrinology Unit, Istanbul University, Istanbul, Turkey; 6Diyarbakır Gazi Yaşargil Training and Research Hospital, Clinic of Pediatric Endocrinology, Diyarbakır, Turkey; 7Dicle University Faculty of Medicine, Department of Pediatric Endocrinology, Diyarbakır, Turkey; 8Department of Pediatric Endocrinology, Hospital of Firat University, Elazığ, Turkey; 9Bursa Uludag University, Department of Pediatric Endocrinology, Bursa, Turkey; 10Diyarbakır Child Diseases Hospital, Clinic of Pediatric Endocrinology, Diyarbakır, Turkey; 11Clinics of Pediatric Endocrinology, University of Health Sciences, Dr. Sami Ulus Obstetrics and Gynecology and Pediatrics Training and Research Hospital, Ankara, Turkey; 12Department of Pediatric Endocrinology, Aydın Adnan Menderes University Faculty of Medicine, Aydın, Turkey; 13Department of Pediatric Endocrinology, Konya Training and Research Hospital, Konya, Turkey; 14Division of Pediatric Endocrinology, University Health of Science, Ankara City Hospital, Ankara, Turkey; 15Department of Pediatric Endocrinology, Ankara Yıldırım Beyazıt University, Ankara, Turkey; 16Dokuz Eylül University, Faculty of Medicine, Division of Pediatric Endocrinology, İzmir, Turkey; 17Department of Pediatric Endocrinology, Health Sciences University Istanbul Bağcılar Training and Research Hospital, Istanbul, Turkey; 18Division of Pediatric Endocrinology, Necmettin Erbakan University Faculty of Medicine, Konya, Turkey; 19Division of Pediatric Endocrinology, Dr. Behçet Uz Children's Education and Research Hospital, İzmir, Turkey; 20Department of Pediatric Endocrinology, University of Health Sciences, Ümraniye Training and Research Hospital, Istanbul, Turkey; 21Division of Pediatric Endocrinology, Faculty of Medicine, Cukurova University, Adana, Turkey; 22Department of Paediatric Endocrinology, Antalya Training and Research Hospital, Antalya, Turkey
Background: Vitamin D Dependent Rickets Type IA(VDDR1a) is an autosomal recessive disorder characterized by defects in the biosynthesis of its active form 1,25 dihydroxyvitamin D due to the mutations in the CYP27B1 gene encoding for the enzyme 1α-hydroxylase.
Objective and hypotheses: To evaluatethe clinical characteristics, molecular genetics aetiology and long-term outcome of a large nationwide cohort of VDDR-Ia from Turkey.
Method: In this nationwide multi-centre retrospective cross-sectional study we collected data from around the country using a web-based research network, CEDD-NET for paediatric endocrinology. Presenting symptoms, family history, gender, age of diagnosis, anthropometric measurements, presence of skeletal deformity, serum Ca, P, ALP, PTH, 25 (OH) vitamin D level, urinary ca/creatinine ratio and radiological findings were collected from the paediatric endocrine centres using a structured dataset disseminated through the CEDD-NET. Molecular genetics analysis results for which a molecular genetic analysis was applicable were collected. Clinical and biochemical characteristics and their relationship with molecular genetics analysis, treatment strategies and long-term outcomes of patients were recorded. Data collected from the paediatric endocrine centres were analysed using IBM-SPSS software.
Results: In total 128 patients (55 F, 73 M) with VDDR1a were recruited. The median age of the diagnosis was 2.0 years. The most common presenting complaints were skeletal deformity (n=48), short stature (n=46), and delay in walking (n=42), The most common mutations detected in molecular genetics analysis were a splice donor sitemutation (c.195+2T>G) (n=38), followed by a 7-bp duplication mutation 1319–1325dupCCCACCC(Phe443Profs*24) (n=20) and the missense p.192K>E(c.574A>G) mutation (n=19), suggesting Turkey serving as a mutational hot spot or founder effect for the relevant variants. All patients were treated using an active form of vitamin D, calcitriol, at a mean daily dose of 56±27 pg/kg and calcium replacement once required. After an average duration of 6 years for calcitriol therapy, patients’ height SDS improved from the baseline (-2.2±1.6) to the latest follow-up visit (1.6±1.4 SD) during the study period (P<0.001) suggesting a favourable long-term outcome. No severe side effect has been reported in the short-term and long-term follow-up undercalcitriol therapy.
Conclusion: In this nationwide multi-centre retrospective cross-sectional study on the VDDR1a most common three mutations accounted for about half of the cohort suggesting Turkey to be a mutational hotspot or founder effect for the relevant variants. Long-term follow-up data revealed improvement in height outcome with no severe complications suggesting a safe and effective therapy with calcitriol treatment.
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