A clinician's guide to X‐linked hypophosphatemia

X‐linked hypophosphatemia (XLH) is the prototypic disorder of renal phosphate wasting, and the most common form of heritable rickets. Physicians, patients, and support groups have all expressed concerns about the dearth of information about this disease and the lack of treatment guidelines, which frequently lead to missed diagnoses or mismanagement. This perspective addresses the recommendation by conferees for the dissemination of concise and accessible treatment guidelines for clinicians arising from the Advances in Rare Bone Diseases Scientific Conference held at the NIH in October 2008. We briefly review the clinical and pathophysiologic features of the disorder and offer this guide in response to the conference recommendation, based on our collective accumulated experience in the management of this complex disorder. © 2011 American Society for Bone and Mineral Research.

[1]  M. Econs,et al.  Familial Hypophosphatemia and Related Disorders , 2012 .

[2]  K. Rosenblatt,et al.  Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[3]  E. Farrow,et al.  Recent advances in renal phosphate handling , 2010, Nature Reviews Nephrology.

[4]  V. Chalifa-Caspi,et al.  Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene. , 2010, American journal of human genetics.

[5]  T. Shimada,et al.  Therapeutic Effects of Anti‐FGF23 Antibodies in Hypophosphatemic Rickets/Osteomalacia , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  C. Macica,et al.  Survey of the Enthesopathy of X-Linked Hypophosphatemia and Its Characterization in Hyp Mice , 2009, Calcified Tissue International.

[7]  Jason R. Stubbs,et al.  Calcimimetics as an adjuvant treatment for familial hypophosphatemic rickets. , 2008, Clinical journal of the American Society of Nephrology : CJASN.

[8]  O. Mäkitie,et al.  Metabolic Control and Growth during Exclusive Growth Hormone Treatment in X-Linked Hypophosphatemic Rickets , 2008, Hormone Research in Paediatrics.

[9]  J. Pettifor.  What’s new in hypophosphataemic rickets? , 2008, European Journal of Pediatrics.

[10]  G. Ariceta,et al.  Growth in X-linked hypophosphatemic rickets , 2007, European Journal of Pediatrics.

[11]  K. Okawa,et al.  Klotho converts canonical FGF receptor into a specific receptor for FGF23 , 2006, Nature.

[12]  T. Strom,et al.  DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis , 2006, Nature Genetics.

[13]  L. Bonewald,et al.  Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism , 2006, Nature Genetics.

[14]  E. Novais,et al.  Hypophosphatemic Rickets: The Role of Hemiepiphysiodesis , 2006, Journal of pediatric orthopedics.

[15]  D. Haffner,et al.  Disproportionate growth following long-term growth hormone treatment in short children with X-linked hypophosphataemia , 1995, European Journal of Pediatrics.

[16]  O. Mäkitie,et al.  Growth and Metabolic Control during Puberty in Girls with X-Linked Hypophosphataemic Rickets , 2004, Hormone Research in Paediatrics.

[17]  Y. Takeuchi,et al.  FGF‐23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[18]  O. Mäkitie,et al.  Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets. , 2003, The Journal of clinical endocrinology and metabolism.

[19]  R. Terkeltaub,et al.  Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification , 2003, Nature Genetics.

[20]  O. Mäkitie,et al.  Prolonged high‐dose phosphate treatment: a risk factor for tertiary hyperparathyroidism in X‐linked hypophosphatemic rickets , 2003, Clinical endocrinology.

[21]  I. Holm,et al.  CHAPTER 25 – Familial Hypophosphatemia and Related Disorders , 2003 .

[22]  T. Meitinger,et al.  Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23 , 2000, Nature Genetics.

[23]  Sochett,et al.  A trial of growth hormone therapy in well‐controlled hypophosphataemic rickets , 1999, Clinical endocrinology.

[24]  M. Marcinkiewicz,et al.  Pex mRNA Is Localized in Developing Mouse Osteoblasts and Odontoblasts , 1998, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[25]  M. Baum,et al.  The effect of recombinant human growth hormone in children with X-linked hypophosphatemia. , 1997, Pediatrics.

[26]  T. Carpenter.  New perspectives on the biology and treatment of X-linked hypophosphatemic rickets. , 1997, Pediatric clinics of North America.

[27]  C. Goodyer,et al.  Pex/PEX tissue distribution and evidence for a deletion in the 3' region of the Pex gene in X-linked hypophosphatemic mice. , 1997, The Journal of clinical investigation.

[28]  G. Addison,et al.  Acute biochemical effects of growth hormone treatment compared with conventional treatment in familial hypophosphataemic rickets , 1996, Clinical endocrinology.

[29]  H. Tenenhouse,et al.  Renal Na(+)-phosphate cotransporter gene expression in X-linked Hyp and Gy mice. , 1996, Kidney international.

[30]  G. Saggese,et al.  Long-term growth hormone treatment in children with renal hypophosphatemic rickets: effects on growth, mineral metabolism, and bone density. , 1995, The Journal of pediatrics.

[31]  A. Poustka,et al.  A gene (PEX) with homologies to endopeptidases is mutated in patients with X–linked hypophosphatemic rickets , 1995, Nature Genetics.

[32]  A. Daneman,et al.  Nephrocalcinosis in X-linked hypophosphataemic rickets: its relationship to treatment, kidney function, and growth. , 1994, Clinical and investigative medicine. Medecine clinique et experimentale.

[33]  F. Glorieux,et al.  A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy in symptomatic adults with X-linked hypophosphatemic rickets. , 1992, The Journal of clinical endocrinology and metabolism.

[34]  F. Schranck,et al.  X‐linked hypophosphatemic rickets: A study (with literature review) of linear growth response to calcitriol and phosphate therapy , 1992, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[35]  J. Simpson,et al.  Effects of therapy in X-linked hypophosphatemic rickets. , 1991, The New England journal of medicine.

[36]  D. Wilson,et al.  Growth hormone therapy in hypophosphatemic rickets. , 1991, American journal of diseases of children.

[37]  V. Chinchilli,et al.  Renal hypophosphatemic rickets. Growth and mineral metabolism after treatment with calcitriol (1,25-dihydroxyvitamin D3) and phosphate supplementation. , 1987, American journal of diseases of children.

[38]  J. Harrelson,et al.  Healing of bone disease in X-linked hypophosphatemic rickets/osteomalacia. Induction and maintenance with phosphorus and calcitriol. , 1985, The Journal of clinical investigation.

[39]  H. DeLuca,et al.  Long-term influence of calcitriol (1,25-dihydroxyvitamin D) and supplemental phosphate in X-linked hypophosphatemic rickets. , 1983, Pediatrics.

[40]  H. Rasmussen,et al.  Long-term treatment of familial hypophosphatemic rickets with oral phosphate and 1α-hydroxyvitamin D3 , 1981 .

[41]  F. Glorieux,et al.  X-linked hypophosphatemia: effect of calcitriol on renal handling of phosphate, serum phosphate, and bone mineralization. , 1981, The Journal of clinical endocrinology and metabolism.

[42]  H. Rasmussen,et al.  Long-term treatment of familial hypophosphatemic rickets with oral phosphate and 1 alpha-hydroxyvitamin D3. , 1981, The Journal of pediatrics.

[43]  F. Glorieux,et al.  Bone response to phosphate salts, ergocalciferol, and calcitriol in hypophosphatemic vitamin D-resistant rickets. , 1980, The New England journal of medicine.

[44]  J. Chan,et al.  Renal hypophosphatemic rickets: growth acceleration after long-term treatment with 1,25-dihydroxyvitamin-D3. , 1980, Pediatrics.