학술논문
Nationwide Turkish Cohort Study of Hypophosphatemic Rickets
ORIGINAL ARTICLE
ORIGINAL ARTICLE
Document Type
Report
Author
Siklar, Zeynep; Turan, Serap; Bereket, Abdullah; Bas, Firdevs; Guran, Tulay; Akberzade, Azad; Abaci, Ayhan; Demir, Korcan; Bober, Ece; Nuri Ozbek, Mehmet; Kara, Cengiz; Poyrazoglu, Sukran; Aydin, Murat; Kardelen, Asli; Tarim, Omer; Eren, Erdal; Hatipoglu, Nihal; Buyukinan, Muammer; Akyurek, Nesibe; Cetinkaya, Semra; Bayramoglu, Elvan; Selver Eklioglu, Beray; Ucakturk, Ahmet; Abali, Saygin; Goksen, Damla; Kor, Yilmaz; Unal, Edip; Esen, Ihsan; Yildirim, Ruken; Akin, Onur; Cayir, Atilla; Dilek, Emine; Kirel, Birgul; Anik, Ahmet; Catli, Gonul; Berberoglu, Merih
Source
Journal of Clinical Research in Pediatric Endocrinology. June 2020, Vol. 12 Issue 2, p150, 10 p.
Subject
Language
English
ISSN
1308-5727
Abstract
Introduction Hypophosphatemic rickets (HR) is a rare renal phosphate-wasting disorder caused by several genetic mutations in factors leading to increase in fibroblast growth factor 23 (FGF23) signalling or secretion, and [...]
What is already known on this topic? Hypophosphatemic rickets (HR) is a rare renal phosphate wasting disorder commonly with X-linked inheritance. There is no nationwide data on HR with initial and follow-up findings. What this study adds? The age of diagnosis was similar in good and bad responders to conventional therapy. Good responders had better height standard deviation score on admission. Higher treatment doses led to nephrocalcinosis without any change in serum levels of phosphorus. Awareness of the importance of early diagnosis and treatment complications should be improved. 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[+ or -]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. Keywords: Hypophosphatemic rickets, PHEX, treatment
What is already known on this topic? Hypophosphatemic rickets (HR) is a rare renal phosphate wasting disorder commonly with X-linked inheritance. There is no nationwide data on HR with initial and follow-up findings. What this study adds? The age of diagnosis was similar in good and bad responders to conventional therapy. Good responders had better height standard deviation score on admission. Higher treatment doses led to nephrocalcinosis without any change in serum levels of phosphorus. Awareness of the importance of early diagnosis and treatment complications should be improved. 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[+ or -]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. Keywords: Hypophosphatemic rickets, PHEX, treatment