Details of Disease

General Information of Disease (ID: DISU3OP6)

• Disease Name: X-linked dominant hypophosphatemic rickets
• Synonyms: hypophophatemic vitamin D-resistant rickets; XLHR; hypophophatemia, X-linked; hypophosphatemic vitamin D-resistant rickets; hypophosphatemic rickets, X-linked dominant; hypophosphatemia, X-linked; HPDR; HYP; X-linked hypophosphatemia; X-linked hypophosphatemic rickets; hypophosphatemic rickets, X-linked dominant, X-linked dominant; hypophosphatemia, vitamin D-resistant rickets; X-linked hereditary hypophosphatemic rickets; rickets, vitamin D-resistant; hypophosphatemic rickets X-linked dominant; X-linked dominant hypophosphatemic rickets; XLH; hereditary hypophosphatemic rickets, X-linked; hypophosphatemic rickets, X-linked; vitamin D-resistant rickets, X-linked
• Definition: X-linked hypophosphatemia (XLH) is a hereditary renal phosphate-wasting disorder characterized by hypophosphatemia, rickets and/or osteomalacia, and diminished growth.
• Disease Hierarchy:
  DISFTLIR: X-linked hypophosphatemic rickets
  DIS5A054: Abnormal mineralization disorder
  DISFHXFA: Hereditary hypophosphatemic rickets
  DIS3ZBO8: X-linked dominant disease
  DISU3OP6: X-linked dominant hypophosphatemic rickets
• Disease Identifiers:
  MONDO ID: MONDO_0010619
  MESH ID: D053098
  UMLS CUI: C0733682
  OMIM ID: 307800
  MedGen ID: 196551
  Orphanet ID: 89936

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Ergocalciferol	DMHO0AR	Approved	Small molecular drug	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BPI	TTXCSDR	Strong	Biomarker	[2]
FGF23	TT2IZ4K	Strong	Biomarker	[3]
SLC22A12	TTA592U	Strong	Biomarker	[4]
SLC9A3	TTFZVPO	Strong	Biomarker	[4]
SOST	TTYRO4F	Strong	Biomarker	[3]

This Disease Is Related to 3 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC17A1	DT8ARWJ	moderate	Biomarker	[5]
SLC34A1	DT42EWA	Strong	Biomarker	[6]
SLC34A3	DTKS517	Strong	Altered Expression	[7]

This Disease Is Related to 9 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
RELB	OTU3QYEF	Limited	Genetic Variation	[8]
BGLAP	OTK1YLWQ	Strong	Genetic Variation	[9]
DMP1	OTBWBWW7	Strong	Genetic Variation	[10]
GLRA2	OTDQ0KW7	Strong	Biomarker	[11]
MEPE	OTXJRUW0	Strong	Biomarker	[12]
RAPGEF5	OT53VS75	Strong	Biomarker	[9]
SCG5	OTXSJMT1	Strong	Altered Expression	[13]
SKA1	OTDYJ12A	Strong	Biomarker	[14]
PHEX	OTG7N3J7	Definitive	X-linked	[15]

References

• [1] Ergocalciferol FDA Label
• [2] Qualitative Research to Explore the Patient Experience of X-Linked Hypophosphatemia and Evaluate the Suitability of the BPI-SF and WOMAC as Clinical Trial End Points.Value Health. 2018 Aug;21(8):973-983. doi: 10.1016/j.jval.2018.01.013. Epub 2018 Jun 6.
• [3] Sclerostin Antibody Treatment Increases Bone Mass and Normalizes Circulating Phosphate Levels in Growing Hyp Mice.J Bone Miner Res. 2020 Mar;35(3):596-607. doi: 10.1002/jbmr.3923. Epub 2019 Dec 10.
• [4] Evidence for a role of PDZ domain-containing proteins to mediate hypophosphatemia in calcium stone formers.Nephrol Dial Transplant. 2018 May 1;33(5):759-770. doi: 10.1093/ndt/gfx284.
• [5] Chromosomal localization of the human renal sodium phosphate transporter to chromosome 5: implications for X-linked hypophosphatemia.Pediatr Res. 1994 Apr;35(4 Pt 1):510-3.
• [6] Renal Na(+)-phosphate cotransporter gene expression in X-linked Hyp and Gy mice.Kidney Int. 1996 Apr;49(4):1027-32. doi: 10.1038/ki.1996.149.
• [7] A case of X-linked hypophosphatemic rickets: complications and the therapeutic use of cinacalcet.Eur J Endocrinol. 2008 Dec;159 Suppl 1:S101-5. doi: 10.1530/EJE-08-0383. Epub 2008 Sep 5.
• [8] 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 Jun;21(6):886-94. doi: 10.1359/jbmr.060307.
• [9] Congenital hypophosphataemia in adults: determinants of bone turnover markers and amelioration of renal phosphate wasting following total parathyroidectomy.J Bone Miner Metab. 2019 Jul;37(4):685-693. doi: 10.1007/s00774-018-0957-5. Epub 2018 Sep 20.
• [10] Hypophosphatemic rickets accelerate chondrogenesis and cell trans-differentiation from TMJ chondrocytes into bone cells via a sharp increase in -catenin.Bone. 2020 Feb;131:115151. doi: 10.1016/j.bone.2019.115151. Epub 2019 Nov 18.
• [11] Fine structure mapping of the human X-linked hypophosphatemic rickets gene locus.J Clin Endocrinol Metab. 1994 Nov;79(5):1351-4. doi: 10.1210/jcem.79.5.7962329.
• [12] FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization.Am J Physiol Endocrinol Metab. 2003 Jul;285(1):E1-9. doi: 10.1152/ajpendo.00016.2003.
• [13] Hexa-D-arginine treatment increases 7B2PC2 activity in hyp-mouse osteoblasts and rescues the HYP phenotype.J Bone Miner Res. 2013 Jan;28(1):56-72. doi: 10.1002/jbmr.1738.
• [14] Overexpression of human PHEX under the human beta-actin promoter does not fully rescue the Hyp mouse phenotype.J Bone Miner Res. 2005 Jul;20(7):1149-60. doi: 10.1359/JBMR.050212. Epub 2005 Feb 21.
• [15] Whole exome sequencing unravels disease-causing genes in consanguineous families in Qatar. Clin Genet. 2014 Aug;86(2):134-41. doi: 10.1111/cge.12280. Epub 2013 Oct 13.