Details of Disease

General Information of Disease (ID: DISZHFC3)

• Disease Name: Vitamin D-dependent rickets, type 2
• Synonyms: vitamin D-dependent rickets type II; vitamin D-dependent rickets, type 2; VDRR II; hypocalcemic vitamin D-resistant rickets; hereditary vitamin D-resistant rickets; VDDR II; VDDR2; vitamin D receptor deficiency; HVDRR; hereditary 1,25 dihydroxyvitamin D-resistant rickets with abnormal Vitamin D receptor; vitamin D dependent rickets 2; vitamin D-resistant rickets type II
• Definition: Hypocalcemic vitamin D-resistant rickets (HVDRR) is a hereditary disorder of vitamin D action characterized by hypocalcemia, severe rickets and in many cases alopecia.|Editor note: ORDO uses dependent-vs-resistant to name types 2 and 1. NCIT seems to confuse type 2 with type 2A
• Disease Hierarchy:
  DIS1S2RY: Hypocalcemic rickets
  DISC3UAJ: Vitamin D-dependent rickets
  DISZHFC3: Vitamin D-dependent rickets, type 2
• Disease Identifiers:
  MONDO ID: MONDO_0019642
  MESH ID: D053098
  UMLS CUI: C3536983
  MedGen ID: 760752
  Orphanet ID: 93160
  SNOMED CT ID: 72831007

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 8 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
VDR	OTFC7K35	Supportive	Autosomal recessive	[1]
MEPE	OTXJRUW0	Limited	Biomarker	[11]
RELB	OTU3QYEF	Limited	Genetic Variation	[12]
CLCN5	OT9YXZSO	Strong	Biomarker	[13]
DMP1	OTBWBWW7	Strong	Genetic Variation	[14]
FGF20	OTJIQ8YZ	Strong	Altered Expression	[4]
SGK3	OTQ6QO99	Strong	Genetic Variation	[15]
FAM20C	OTW5YZ7X	Definitive	Genetic Variation	[16]

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
VDR	TTK59TV	Supportive	Autosomal recessive	[1]
AVPR2	TTK8R02	Strong	Genetic Variation	[2]
CYP24A1	TT82UI1	Strong	Biomarker	[3]
FGF14	TTKJX1V	Strong	Altered Expression	[4]
VDR	TTK59TV	Strong	Genetic Variation	[5]
ENPP1	TTZTIWS	Definitive	Genetic Variation	[6]
PTH	TT6F7GZ	Definitive	Altered Expression	[7]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC2A2	DTUJPOL	Strong	Altered Expression	[8]
SLC34A3	DTKS517	Strong	Genetic Variation	[9]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CYP27B1	DE3FYEM	Definitive	Genetic Variation	[10]

References

• [1] Mutations in the vitamin D receptor gene in three kindreds associated with hereditary vitamin D resistant rickets. J Clin Endocrinol Metab. 1997 Sep;82(9):3156-60. doi: 10.1210/jcem.82.9.4243.
• [2] 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.
• [3] CYP24 inhibition as a therapeutic target in FGF23-mediated renal phosphate wasting disorders.J Clin Invest. 2016 Feb;126(2):667-80. doi: 10.1172/JCI81928. Epub 2016 Jan 19.
• [4] Molecular pathology of the fibroblast growth factor family.Hum Mutat. 2009 Sep;30(9):1245-55. doi: 10.1002/humu.21067.
• [5] Vitamin D-Resistant Rickets and Cinacalcet-One More Favorable Experience.Front Pediatr. 2018 Nov 28;6:376. doi: 10.3389/fped.2018.00376. eCollection 2018.
• [6] 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.
• [7] FGF23 expression is stimulated in transgenic -Klotho longevity mouse model.JCI Insight. 2019 Dec 5;4(23):e132820. doi: 10.1172/jci.insight.132820.
• [8] 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.
• [9] 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.
• [10] Presence of a deletion mutation (c.716delA) in the ligand binding domain of the vitamin D receptor in an Indian patient with vitamin D-dependent rickets type II.Calcif Tissue Int. 2010 Jan;86(1):33-41. doi: 10.1007/s00223-009-9310-2. Epub 2009 Nov 17.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Mutation of SGK3, a Novel Regulator of Renal Phosphate Transport, Causes Autosomal Dominant Hypophosphatemic Rickets.J Clin Endocrinol Metab. 2020 Jun 1;105(6):dgz260. doi: 10.1210/clinem/dgz260.
• [16] Exome sequencing reveals FAM20c mutations associated with fibroblast growth factor 23-related hypophosphatemia, dental anomalies, and ectopic calcification.J Bone Miner Res. 2013 Jun;28(6):1378-85. doi: 10.1002/jbmr.1850.