Nationwide Turkish Cohort Study of Hypophosphatemic Rickets
Zeynep Şıklar1, Serap Turan2, Abdullah Bereket2, Firdevs Baş3, Tülay Güran2, Azad Akberzade2, Ayhan Abacı4, Korcan Demir4, Ece Böber4, Mehmet Nuri Özbek5, Cengiz Kara6, Şükran Poyrazoğlu3, Murat Aydın6, Aslı Kardelen3, Ömer Tarım7, Erdal Eren7, Nihal Hatipoğlu8, Muammer Büyükinan9, Nesibe Akyürek9, Semra Çetinkaya10, Elvan Bayramoğlu10, Beray Selver Eklioğlu11, Ahmet Uçaktürk12, Saygın Abalı13, Damla Gökşen14, Yılmaz Kor15, Edip Ünal16, İhsan Esen17, Ruken Yıldırım18, Onur Akın19, Atilla Çayır20, Emine Dilek21, Birgül Kırel22, Ahmet Anık23, Gönül Çatlı24, Merih Berberoğlu11Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, Turkey2Marmara University Pendik Training and Reseach Hospital, Clinic of Pediatric Endocrinology, İstanbul, Turkey
3İstanbul University Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey
4Dokuz Eylül University Faculty of Medicine, Department of Pediatric Endocrinology, İzmir, Turkey
5University of Health Sciences Turkey, Gazi Yaşargil Training and Research Hospital, Clinic of Pediatric Endocrinology, Diyarbakır, Turkey
6Ondokuz Mayıs University Faculty of Medicine, Department of Pediatric Endocrinology, Samsun, Turkey
7Uludağ University Faculty of Medicine, Department of Pediatric Endocrinology, Bursa, Turkey
8Erciyes University Faculty of Medicine, Department of Pediatric Endocrinology, Kayseri, Turkey
9Konya Training and Research Hospital, Clinic of Pediatric Endocrinology, Konya, Turkey
10University of Health Sciences Turkey, Ankara Dr. Sami Ulus Obstetrics and Pediatrics Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey
11Necmettin Erbakan University, Meram Faculty of Medicine, Department of Pediatric Endocrinology, Konya, Turkey
12Ankara City Hospital, Children’s Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey
13İstanbul Kartal Dr. Lütfi Kırdar Training and Research Hospital, Clinic of Pediatric Endocrinology, İstanbul, Turkey
14Ege University Faculty of Medicine, Department of Pediatric Endocrinology, İzmir, Turkey
15University of Health Sciences Turkey, Adana Numune Training and Research Hospital, Clinic of Pediatric Endocrinology, Adana, Turkey
16Dicle University Faculty of Medicine, Department of Pediatric Endocrinology, Diyarbakır, Turkey
17Fırat University Faculty of Medicine, Department of Pediatric Endocrinology, Elazığ, Turkey
18Diyarbakır Children Hospital, Clinic of Pediatric Endocrinology, Diyarbakır, Turkey
19University of Health Sciences Turkey, Gülhane Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey
20Erzurum Training and Research Hospital, Clinic of Pediatric Endocrinology, Erzurum, Turkey
21Trakya University Faculty of Medicine, Department of Pediatric Endocrinology, Edirne, Turkey
22Eskişehir Osmangazi University Faculty of Medicine, Department of Pediatric Endocrinology, Eskişehir, Turkey
23Aydın Adnan Menderes University Faculty of Medicine, Department of Pediatric Endocrinology, Aydın, Turkey
24İzmir Katip Çelebi Faculty of Medicine, Department of Pediatric Endocrinology, İzmir, Turkey
Objective: Hypophosphatemic rickets (HR) is a rare renal phosphate-wasting disorder, which is usually X-linked and is commonly caused by PHEX mutations. The treatment and follow-up of HR is challenging due to imperfect treatment options.
Methods: Here we present nationwide initial and follow-up data on HR.
Results: From 24 centers, 166 patients were included in the study. Genetic analysis (n=75) showed PHEX mutation in 80% of patients. The mean follow-up period was 6.7±2.4 years. During the first 3-years of treatment (n=91), mild increase in phosphate, decrease in alkaline phosphatase and elevation in parathyroid hormone (PTH) levels were detected. The height standard deviation scores were -2.38, -2.77, -2.72, -2.47 at initial, 1st, 2nd and 3rd year of treatment, respectively (p>0.05). On follow-up 36% of the patients showed complete or significant improvement in leg deformities and these patients had similar phosphate levels at presentation with better levels in 1st and 2nd years of treatment; even the treatment doses of phosphate were similar. Furthermore, 27 patients developed nephrocalcinosis (NC), the patients showed no difference in biochemical differences at presentation and follow-up, but 3rd year PTH was higher. However, higher treatment doses of phosphate and calcitriol were found in the NC group.
Conclusion: HR treatment and follow-up is challenging and our results showed higher treatment doses were associated with NC without any change in serum phosphate levels, suggesting that giving higher doses led to increased phosphaturia, probably through stimulation of fibroblast growth factor 23. However, higher calcitriol doses could improve bone deformities. Safer and more efficacious therapies are needed.
Manuscript Language: English
