familial hypophosphatemia

Summary

Summary: An inherited condition of abnormally low serum levels of PHOSPHATES (below 1 mg/liter) which can occur in a number of genetic diseases with defective reabsorption of inorganic phosphorus by the PROXIMAL RENAL TUBULES. This leads to phosphaturia, HYPOPHOSPHATEMIA, and disturbances of cellular and organ functions such as those in X-LINKED HYPOPHOSPHATEMIC RICKETS; OSTEOMALACIA; and FANCONI SYNDROME.

Top Publications

  1. Beck Nielsen S, Brock Jacobsen B, Gram J, Brixen K, Jensen T. Incidence and prevalence of nutritional and hereditary rickets in southern Denmark. Eur J Endocrinol. 2009;160:491-7 pubmed publisher
    ..To estimate the incidence of nutritional rickets and the incidence and prevalence of hereditary rickets...
  2. Savio R, Gosnell J, Posen S, Reeve T, Delbridge L. Parathyroidectomy for tertiary hyperparathyroidism associated with X-linked dominant hypophosphatemic rickets. Arch Surg. 2004;139:218-22 pubmed
    ..We report our surgical experience with 6 patients with XLHR who underwent parathyroidectomy for associated autonomous parathyroid hyperfunction...
  3. Pereira C, de Andrade C, Vargas P, Coletta R, de Almeida O, Lopes M. Dental alterations associated with X-linked hypophosphatemic rickets. J Endod. 2004;30:241-5 pubmed
    ..We present three patients from the same family with X-linked hypophosphatemic rickets showing bone and dental alterations...
  4. Meyer R, Gray R, Meyer M. Abnormal vitamin D metabolism in the X-linked hypophosphatemic mouse. Endocrinology. 1980;107:1577-81 pubmed
    ..We conclude that Hyp mice have a defective control system for plasma levels of 1,25-(OH)2D that does not respond to a low P stimulus with elevated plasma levels of the hormone...
  5. Sepahi M, Heidari A, Shajari A. Clinical manifestations and etiology of renal stones in children less than 14 years age. Saudi J Kidney Dis Transpl. 2010;21:181-4 pubmed
    ..Family history of urolithiasis was found in 23% of patients and 54% presented with urinary tract infection (UTI). We conclude that majority of patients were symptomatic and hypocitraturia was the commenest risk factor among others...
  6. Tanaka H. [X-linked hypophosphatemic vitamin D resistant rickets: Pathogenesis, pathophysiology, and therapy]. Nihon Rinsho. 2006;64 Suppl 2:556-61 pubmed
  7. Dobbie H, Unwin R, Faria N, Shirley D. Matrix extracellular phosphoglycoprotein causes phosphaturia in rats by inhibiting tubular phosphate reabsorption. Nephrol Dial Transplant. 2008;23:730-3 pubmed
    ..To date, its effect on renal tubular phosphate reabsorption remains undefined...
  8. Beraud G, Perimenis P, Velayoudom F, Wemeau J, Vantyghem M. [Genetic hypophosphatemia: recent advances in physiopathogenic concept]. Ann Endocrinol (Paris). 2005;66:109-16 pubmed
    ..According recent data, FGF23, MEPE (Matrix Extracellular Phosphoglycoprotein) et FRP4 (frizzled related protein-4) are 3 putative "phosphatonines"...
  9. Cho H, Lee B, Kang J, Ha I, Cheong H, Choi Y. A clinical and molecular genetic study of hypophosphatemic rickets in children. Pediatr Res. 2005;58:329-33 pubmed
    ..No genotype-phenotype correlation in XLH was detected in this study, but a large-scaled study on this topic is warranted. The large proportion of patients with a normal genetic study suggests the possibility of other causative gene(s)...

More Information

Publications62

  1. Fishman G, Miller Hansen D, Jacobsen C, Singhal V, Alon U. Hearing impairment in familial X-linked hypophosphatemic rickets. Eur J Pediatr. 2004;163:622-3 pubmed
  2. Saggese G, Baroncelli G. Hypophosphataemic rickets. Horm Res. 2000;53 Suppl 3:57-60 pubmed
    ..In some poorly growing XLH patients, long-term GH treatment associated with conventional therapy improves linear growth. GH treatment also increases phosphate retention but this effect is transient...
  3. McClanahan S, Wilson J, Anderson K. What is your diagnosis? Hypophosphatemic rickets as a consequence of hypovitaminosis D. J Am Vet Med Assoc. 2006;229:499-500 pubmed
  4. Fukumoto S. [Tumor-induced rickets/osteomalacia]. Nihon Rinsho. 2005;63 Suppl 10:523-8 pubmed
  5. Lin N, Malloy P, Sakati N, Al Ashwal A, Feldman D. A novel mutation in the deoxyribonucleic acid-binding domain of the vitamin D receptor causes hereditary 1,25-dihydroxyvitamin D-resistant rickets. J Clin Endocrinol Metab. 1996;81:2564-9 pubmed
    ..In conclusion, a new mutation was identified in exon 2 of the VDR gene. This mutation, which occurs in the first zinc finger of the DNA-binding domain of the receptor, blocks 1,25-(OH)2D3 action and leads to the syndrome of HVDRR...
  6. Ward L. Renal phosphate--wasting disorders in childhood. Pediatr Endocrinol Rev. 2005;2 Suppl 3:342-50 pubmed
    ..The information may be invaluable in the complex diagnosis and successful treatment of OHO and hereditary hypophosphatemias of childhood...
  7. Kempe D, Dërmaku Sopjani M, Fröhlich H, Sopjani M, Umbach A, Puchchakayala G, et al. Rapamycin-induced phosphaturia. Nephrol Dial Transplant. 2010;25:2938-44 pubmed publisher
    ..The present study was performed to elucidate whether mTOR similarly regulates the major renal tubular phosphate transporter NaPi-IIa...
  8. Ozono K. [Bone and joint diseases in children. Phosphaturic hormone, FGF23, and bone metabolism]. Clin Calcium. 2010;20:896-903 pubmed publisher
    ..Alpha klotho, originally discovered as an anti-aging factor, along with the FGF receptor type 1 makes a specific receptor for FGF23...
  9. Brun Heath I, Lia Baldini A, Maillard S, Taillandier A, Utsch B, Nunes M, et al. Delayed transport of tissue-nonspecific alkaline phosphatase with missense mutations causing hypophosphatasia. Eur J Med Genet. 2007;50:367-78 pubmed
    ..We concluded that reduced ALP activity of these TNSALP mutants results from structural disturbances and delay in membrane anchoring, and not from compromised catalytic activity...
  10. McHenry C, Mostafavi K, Murphy T. Tertiary hyperparathyroidism attributable to long-term oral phosphate therapy. Endocr Pract. 2006;12:294-8 pubmed
    ..To report a rare case of tertiary hyperparathyroidism (HPT) as a result of long-term oral phosphate therapy...
  11. Plans V, Rickheit G, Jentsch T. Physiological roles of CLC Cl(-)/H (+) exchangers in renal proximal tubules. Pflugers Arch. 2009;458:23-37 pubmed publisher
    ..Loss of ClC-7 or its beta-subunit Ostm1 entails lysosomal storage in the PT, in addition to the neuronal lysosomal storage and osteopetrosis that are the hallmarks of ClC-7/Ostm1 loss in mice and men...
  12. Nguyen M, d Alesio A, Pascussi J, Kumar R, Griffin M, Dong X, et al. Vitamin D-resistant rickets and type 1 diabetes in a child with compound heterozygous mutations of the vitamin D receptor (L263R and R391S): dissociated responses of the CYP-24 and rel-B promoters to 1,25-dihydroxyvitamin D3. J Bone Miner Res. 2006;21:886-94 pubmed
    ..Transfection studies suggest dissociated effects of VDR gene mutations on the regulation of genes involved in vitamin D metabolism and dendritic cell maturation...
  13. Rifas L, Dawson L, Halstead L, Roberts M, Avioli L. Phosphate transport in osteoblasts from normal and X-linked hypophosphatemic mice. Calcif Tissue Int. 1994;54:505-10 pubmed
    ..As osteoblast P(i) uptake and transport is apparently normal in the Hyp mouse model of XLH, the "osteoblastic failure" described for the Hyp mouse should be attributed to other mechanism(s)...
  14. Econs M, McEnery P, Lennon F, Speer M. Autosomal dominant hypophosphatemic rickets is linked to chromosome 12p13. J Clin Invest. 1997;100:2653-7 pubmed
    ..Such studies will permit ultimate identification of the ADHR gene and provide further insight into phosphate homeostasis...
  15. Kelleher C, Buckalew V, Frederickson E, Rhodes D, Conner D, Seidman J, et al. CLCN5 mutation Ser244Leu is associated with X-linked renal failure without X-linked recessive hypophosphatemic rickets. Kidney Int. 1998;53:31-7 pubmed
    ..We hypothesize that genetic background, environment, diet, or an unidentified modifying gene may account for the differing phenotypes resulting from this shared gene defect...
  16. Pettifor J. Rickets. Calcif Tissue Int. 2002;70:398-9 pubmed
  17. Malloy P, Feldman D. Hereditary 1,25-Dihydroxyvitamin D-resistant rickets. Endocr Dev. 2003;6:175-99 pubmed
  18. Ahn J, Kim H, Cha C, Kim J, Yim S, Kim H. Oncogenic osteomalacia: induced by tumor, cured by surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103:636-41 pubmed
  19. Sabbagh Y, Boileau G, Campos M, Carmona A, Tenenhouse H. Structure and function of disease-causing missense mutations in the PHEX gene. J Clin Endocrinol Metab. 2003;88:2213-22 pubmed
    ..Thus, defects in protein trafficking, endopeptidase activity, and protein conformation account for loss of PHEX function in XLH patients harboring these missense mutations...
  20. Tyynismaa H, Kaitila I, Näntö Salonen K, Ala Houhala M, Alitalo T. Identification of fifteen novel PHEX gene mutations in Finnish patients with hypophosphatemic rickets. Hum Mutat. 2000;15:383-4 pubmed
    ..Also, no mutation could be detected in a patient with suspected oncogenic osteomalacia (OHO)...
  21. Chaussain Miller C, Sinding C, Septier D, Wolikow M, Goldberg M, Garabedian M. Dentin structure in familial hypophosphatemic rickets: benefits of vitamin D and phosphate treatment. Oral Dis. 2007;13:482-9 pubmed
  22. Francis F, Strom T, Hennig S, Böddrich A, Lorenz B, Brandau O, et al. Genomic organization of the human PEX gene mutated in X-linked dominant hypophosphatemic rickets. Genome Res. 1997;7:573-85 pubmed
  23. Jacobson J, Kalume Brigido M. Case 97: X-linked hypophosphatemic osteomalacia with insufficiency fracture. Radiology. 2006;240:607-10 pubmed
  24. Gundberg C, Clough M, Carpenter T. Development and validation of a radioimmunoassay for mouse osteocalcin: paradoxical response in the Hyp mouse. Endocrinology. 1992;130:1909-15 pubmed
    ..Our results are consistent with the hypothesis that abnormal osteoblastic activity is present in Hyp mice. Furthermore, hypophosphatemia may be a general regulator of osteocalcin synthesis or secretion in the mouse...
  25. Chung W, Niu D, Lin C. Clinical aspects of X-linked hypophosphatemic rickets. Acta Paediatr Taiwan. 2002;43:26-34 pubmed
    ..Thirteen of 15 cases had elevated alkaline phosphatase activity; two showed hyperparathyroidism. Four cases had sufficient follow-up growth data and had an increase in height percentile and velocity after combination therapy...
  26. Negri A. [Fibroblast growth factor 23 (FGF 23): a new fosfaturic hormone?]. Nefrologia. 2003;23:478-81 pubmed
  27. Rauch F. The rachitic bone. Endocr Dev. 2003;6:69-79 pubmed
  28. Rowe P. The wrickkened pathways of FGF23, MEPE and PHEX. Crit Rev Oral Biol Med. 2004;15:264-81 pubmed
  29. Sato K, Tajima T, Nakae J, Adachi M, Asakura Y, Tachibana K, et al. Three novel PHEX gene mutations in Japanese patients with X-linked hypophosphatemic rickets. Pediatr Res. 2000;48:536-40 pubmed
    ..These results suggest that: 1) PHEX gene mutations are responsible for XLH in Japanese patients, and 2) PHEX gene mutations are heterogeneous in the Japanese population similarly to other ethnic populations...
  30. Muller Y, Collins J, Ghishan F. Genetic screening for X-linked hypophosphatemic mice and ontogenic characterization of the defect in the renal sodium-phosphate transporter. Pediatr Res. 1998;44:633-8 pubmed
    ..This study demonstrates an easy assay to detect Hyp mutation and characterizes the defect during ontogeny of the Na(+)-Pi transporter in Hyp mice...
  31. Sugiyama T, Taguchi T, Kawai S. Adaptation of bone to mechanical loads. Lancet. 2002;359:1160 pubmed
  32. Alpay H, Ozen A, Gokce I, Biyikli N. Clinical and metabolic features of urolithiasis and microlithiasis in children. Pediatr Nephrol. 2009;24:2203-9 pubmed publisher
    ..These results draw attention to the importance of screening for UTIs in patients with urolithiasis...
  33. Tanaka H. [X-linked hypophosphatemic rickets]. Nihon Rinsho. 2006;Suppl 2:120-5 pubmed
  34. Brault B, Meyer M, Meyer R. Malabsorption of phosphate by the intestines of young X-linked hypophosphatemic mice. Calcif Tissue Int. 1988;43:289-93 pubmed
    ..Thus, phosphate malabsorption in Hyp mice is an age-related phenomena. These changes parallel the malabsorption of calcium in young Hyp mice and reflect the lowered plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) levels of young Hyp mice...
  35. Michałus I, Chlebna Sokół D, Rusińska A, Jakubowska Pietkiewicz E, Kulińska Szukalska K. Evaluation of bone mineral density and bone metabolism in children with multiple bone fractures. Ortop Traumatol Rehabil. 2008;10:602-12 pubmed
    ..The aim of the study was to carry out a comprehensive analysis of determinants of multiple bone fractures in children with regard to densitometric indices and markers of bone metabolism...
  36. Baroncelli G, Angiolini M, Ninni E, Galli V, Saggese R, Giuca M. Prevalence and pathogenesis of dental and periodontal lesions in children with X-linked hypophosphatemic rickets. Eur J Paediatr Dent. 2006;7:61-6 pubmed
    ..To assess the prevalence and to investigate the pathogenetic mechanisms of dental and periodontal lesions in children with X-linked hypophosphatemic rickets (XLH) examined at diagnosis or during treatment...
  37. Negri A, Negrotti T, Alonso G, Pasqualini T. [Different forms of clinical presentation of an autosomal dominant hypophosphatemic rickets caused by a FGF23 mutation in one family]. Medicina (B Aires). 2004;64:103-6 pubmed
    ..Genomic DNA analysis performed in patient No 3, showed missense mutation with substitution of arginine at position 179 for glutamine. The family was catalogued as having autosomal dominant hypophosphatemic rickets/osteomalacia...
  38. Grzanka K, Kucharz E. [Vitamin D-resistant rickets]. Wiad Lek. 2004;57:663-71 pubmed
    ..Other forms are as the following: oncogenic hypophosphatemic osteomalacia, autosomal dominant hypophosphatemic rickets, hereditary hypophosphatemic rickets with hypercalciuria and pseudo-vitamin D deficient rickets type I and II...
  39. Chou Y, Chao S, Shiue C, Tsai W, Lin S. Hypophosphatemic rickets associated with epidermal nevus syndrome and giant hairy nevus. J Pediatr Endocrinol Metab. 2005;18:93-5 pubmed
    ..We did not find a PHEX gene mutation in these two patients, and the mechanism for their rickets may be different from that in X-linked hypophosphatemic rickets...
  40. Saraswat A, Dogra S, Bansali A, Kumar B. Phakomatosis pigmentokeratotica associated with hypophosphataemic vitamin D-resistant rickets: improvement in phosphate homeostasis after partial laser ablation. Br J Dermatol. 2003;148:1074-6 pubmed
  41. Xie W, Méchin M, Dubois S, Lajeunesse D, van de Werve G. Up-regulation of liver glucose-6-phosphatase in x-linked hypophosphatemic mice. Horm Metab Res. 2002;34:288-92 pubmed
    ..It is concluded that in genetic as in dietary hypophosphatemia, elevated glucose-6-phosphatase activity could be partially responsible for the impaired glucose metabolism albeit through distinct mechanisms...
  42. Malloy P, Weisman Y, Feldman D. Hereditary 1 alpha,25-dihydroxyvitamin D-resistant rickets resulting from a mutation in the vitamin D receptor deoxyribonucleic acid-binding domain. J Clin Endocrinol Metab. 1994;78:313-6 pubmed
    ..It is unclear at this time whether these kindreds might be distantly related and, therefore, harbor the same mutation, or whether this represents a mutational hot spot in the VDR gene...
  43. Rifas L, Gupta A, Hruska K, Avioli L. Altered osteoblast gluconeogenesis in X-linked hypophosphatemic mice is associated with a depressed intracellular pH. Calcif Tissue Int. 1995;57:60-3 pubmed
  44. Tenenhouse H, Henry H. Protein kinase activity and protein kinase inhibitor in mouse kidney: effect of the X-linked Hyp mutation and vitamin D status. Endocrinology. 1985;117:1719-26 pubmed
  45. Lo F, Kuo M, Wang C, Chang C, Lee Z, Van Y. Two novel PHEX mutations in Taiwanese patients with X-linked hypophosphatemic rickets. Nephron Physiol. 2006;103:p157-63 pubmed
    ..The disease is caused by mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X-chromosome) located at Xp22.1. To date, a variety of PHEX mutations have been identified in these patients...
  46. Novais E, Stevens P. Hypophosphatemic rickets: the role of hemiepiphysiodesis. J Pediatr Orthop. 2006;26:238-44 pubmed
    ..We are presenting the rationale for, and the results of, that surgery, in an effort to define the role of this minimally invasive procedure...
  47. Ciana G, Trappan A, Bembi B, Benettoni A, Maso G, Zennaro F, et al. Generalized arterial calcification of infancy: two siblings with prolonged survival. Eur J Pediatr. 2006;165:258-63 pubmed
    ..In both siblings, spontaneous regression of arterial calcifications occurred, and antihypertensive treatment could be tapered off gradually. In some patients, the natural course of GACI may be more favourable than previously assumed...
  48. Vaisbich M, Koch V. Hypophosphatemic rickets: results of a long-term follow-up. Pediatr Nephrol. 2006;21:230-4 pubmed
    ..A careful protocol is recommended to detect such complications as nephrocalcinosis. We suggest potassium citrate for patients with hypercalciuria to avoid calcium precipitation...
  49. Prie D, Beck L, Urena P, Friedlander G. Recent findings in phosphate homeostasis. Curr Opin Nephrol Hypertens. 2005;14:318-24 pubmed
    ..We summarize the most recent findings on the proteins that interact with sodium/inorganic phosphate (Na/Pi) cotransporters, the factors that regulate Pi homeostasis and their role in pathology...
  50. Yamamoto T, Imanishi Y, Kinoshita E, Nakagomi Y, Shimizu N, Miyauchi A, et al. The role of fibroblast growth factor 23 for hypophosphatemia and abnormal regulation of vitamin D metabolism in patients with McCune-Albright syndrome. J Bone Miner Metab. 2005;23:231-7 pubmed
    ..These data suggested that FGF-23 is a possible causal factor for hypophosphatemia and abnormal vitamin D metabolism in MAS...
  51. Takeda E, Yamamoto H, Nashiki K, Sato T, Arai H, Taketani Y. Inorganic phosphate homeostasis and the role of dietary phosphorus. J Cell Mol Med. 2004;8:191-200 pubmed
    ..In considering the relationship of klotho expression to the dietary Pi level, the klotho protein seemed to be negatively controlled by dietary Pi...
  52. Tokita A, Hisada K, Nishizawa K. [Bone disease with vitamin D receptor abnormality]. Nihon Rinsho. 2002;60:385-90 pubmed
    ..Recently, polymorphism at the VDR locus has been implicated as a genetic marker for bone mineral density. Vitamin D receptor gene start codon polymorphisms, and 3'-end region polymorphisms may modulate bone density...
  53. Scriver C, Tenenhouse H. Conserved loci on the X chromosome confer phosphate homeostasis in mice and humans. Genet Res. 1990;56:141-52 pubmed
    ..The tooth data imply that the X chromosome locus is expressed in both renal and non-renal cells. The polypeptide product of the X chromosome gene(s) is still unknown...