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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Toppari, Jorma

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Volume 28, Issue 9-10


Phosphate homeostasis and genetic mutations of familial hypophosphatemic rickets

Nurul Nadirah Razali
  • Clinical Genetics Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM SERDANG, Selangor Darul Ehsan, Malaysia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ting Tzer Hwu
  • Department of Paediatrics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM SERDANG, Selangor Darul Ehsan, Malaysia.
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Karuppiah Thilakavathy
  • Corresponding author
  • Clinical Genetics Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM SERDANG, Selangor Darul Ehsan, Malaysia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2015-04-18 | DOI: https://doi.org/10.1515/jpem-2014-0366


Hypophosphatemic rickets (HR) is a syndrome of hypophosphatemia and rickets that resembles vitamin D deficiency, which is caused by malfunction of renal tubules in phosphate reabsorption. Phosphate is an essential mineral, which is important for bone and tooth structure. It is regulated by parathyroid hormone, 1,25-dihydroxyvitamin D and fibroblast-growth-factor 23 (FGF23). X-linked hypophosphatemia (XLH), autosomal dominant HR (ADHR), and autosomal recessive HR (ARHR) are examples of hereditary forms of HR, which are mainly caused by mutations in the phosphate regulating endopeptidase homolog, X-linked (PHEX), FGF23, and, dentin matrix protein-1 (DMP1) and ecto-nucleotide pyro phosphatase/phosphodiesterase 1 (ENPP1) genes, respectively. Mutations in these genes are believed to cause elevation of circulating FGF23 protein. Increase in FGF23 disrupts phosphate homeostasis, leading to HR. This review aims to summarize phosphate homeostasis and focuses on the genes and mutations related to XLH, ADHR, and ARHR. A compilation of XLH mutation hotspots based on the PHEX gene database and mutations found in the FGF23, DMP1, and ENPP1 genes are also made available in this review.

Keywords: DMP1; ENPP1; FGF23; hypophosphatemia; hypophosphatemic rickets; PHEX; phosphate homeostasis


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About the article

Corresponding author: Assoc. Prof. Dr. Karuppiah Thilakavathy, Clinical Genetics Unit, Department of Obstetrics and Gynaecology, Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM SERDANG, Selangor Darul Ehsan, Malaysia, Phone: +60389472652, Fax: +60389472646, E-mail:

Received: 2014-08-28

Accepted: 2015-02-26

Published Online: 2015-04-18

Published in Print: 2015-09-01

Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 28, Issue 9-10, Pages 1009–1017, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2014-0366.

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