Details of Disease

General Information of Disease (ID: DIS7XTW5)

• Disease Name: Hypophosphatemic rickets
• Synonyms: hypophosphatemia, vitamin D-resistant rickets; Ricket, hypophosphatemic; rickets, vitamin D resistant; rickets, vitamin D-resistant; hypophosphatemic vitamin D resistant rickets; vitamin D-resistant rickets; hypophosphatemic Ricket; hypophosphatemic vitamin D-resistant rickets; acquired vitamin D-resistant rickets; acquired vitamin D resistant rickets; hypophosphatemic rickets; Phosphopenic rickets
• Disease Class: 5C63: Vitamin/non-protein cofactor absorption/transport disorder
• Definition: Rickets due to low serum phosphate concentrations, the cause of which can be nutritional or genetic. This condition is characterized by normal parathyroid hormone concentrations, usually caused by renal phosphate wasting occurring in isolation or as part of a renal tubular disorder, and characterized by resistance to treatment with ultraviolet radiation or vitamin D.
• Disease Hierarchy:
  DISH89YF: Rickets
  DIS7XTW5: Hypophosphatemic rickets
• ICD Code: ICD-11: ICD-11: 5C63.22
• Disease Identifiers:
  MONDO ID: MONDO_0024300
  MESH ID: D063730
  UMLS CUI: C1704375
  MedGen ID: 309957
  HPO ID: HP:0004912
  SNOMED CT ID: 66266003

Drug-Interaction Atlas (DIA) of This Disease

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
INZ-701	DMNC1AS	Phase 1/2	Enzyme replacement	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ENPP1	TTZTIWS	moderate	Genetic Variation	[2]
AVPR2	TTK8R02	Strong	Genetic Variation	[3]
FGF14	TTKJX1V	Strong	Altered Expression	[4]
NRAS	TTW2R9X	Strong	Genetic Variation	[5]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC2A2	DTUJPOL	Strong	Altered Expression	[6]
SLC34A3	DTKS517	Strong	Genetic Variation	[7]

This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
MEPE	OTXJRUW0	Limited	Biomarker	[8]
PHEX	OTG7N3J7	Limited	Genetic Variation	[9]
SGK3	OTQ6QO99	Limited	Autosomal dominant	[10]
DMP1	OTBWBWW7	moderate	Genetic Variation	[11]
CLCN5	OT9YXZSO	Strong	Biomarker	[12]
FGF20	OTJIQ8YZ	Strong	Altered Expression	[4]

References

• [1] ClinicalTrials.gov (NCT04686175) A Phase 1/2, Open-Label, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INZ-701 Followed by an Open-Label Long-Term Extension Period in Adults With ENPP1 Deficiency. U.S.National Institutes of Health.
• [2] Phosphate homeostasis and genetic mutations of familial hypophosphatemic rickets.J Pediatr Endocrinol Metab. 2015 Sep;28(9-10):1009-17. doi: 10.1515/jpem-2014-0366.
• [3] Familial hypophosphatemic rickets caused by a large deletion in PHEX gene.Eur J Endocrinol. 2009 Oct;161(4):647-51. doi: 10.1530/EJE-09-0261. Epub 2009 Jul 6.
• [4] Molecular pathology of the fibroblast growth factor family.Hum Mutat. 2009 Sep;30(9):1245-55. doi: 10.1002/humu.21067.
• [5] Mosaic NRAS Q61R mutation in a child with giant congenital melanocytic naevus, epidermal naevus syndrome and hypophosphataemic rickets.Clin Exp Dermatol. 2017 Jan;42(1):75-79. doi: 10.1111/ced.12969. Epub 2016 Nov 30.
• [6] Mutation analysis of the GLUT2 gene in three unrelated Egyptian families with Fanconi-Bickel syndrome: revisited gene atlas for renumbering.Clin Exp Nephrol. 2012 Aug;16(4):604-10. doi: 10.1007/s10157-012-0603-9. Epub 2012 Feb 18.
• [7] Hypophosphatemic rickets with hypercalciuria due to mutation in SLC34A3/NaPi-IIc can be masked by vitamin D deficiency and can be associated with renal calcifications.Exp Clin Endocrinol Diabetes. 2009 Feb;117(2):49-56. doi: 10.1055/s-2008-1076716. Epub 2008 Jun 3.
• [8] Clinical and molecular heterogeneity in a large series of patients with hypophosphatemic rickets.Bone. 2015 Oct;79:143-9. doi: 10.1016/j.bone.2015.05.040. Epub 2015 Jun 5.
• [9] Mineralized tissues in hypophosphatemic rickets.Pediatr Nephrol. 2020 Oct;35(10):1843-1854. doi: 10.1007/s00467-019-04290-y. Epub 2019 Aug 8.
• [10] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [11] 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.
• [12] Mutational analysis of PHEX, FGF23 and CLCN5 in patients with hypophosphataemic rickets.Clin Endocrinol (Oxf). 2017 Jul;87(1):103-112. doi: 10.1111/cen.13347. Epub 2017 May 11.