Details of Disease

General Information of Disease (ID: DISH89YF)

• Disease Name: Rickets
• Synonyms: vitamin D deficiency disease; active rickets; nutritional rickets; vitamin-D deficiency rickets; hypovitaminosis D; vitamin D hydroxylation-deficient rickets; rachitis; rickets (disease); rickets
• Disease Class: 5B55-5B5F: Vitamin deficiency
• Definition: Bone softening and weakening usually caused by deficiency or impaired metabolism of vitamin D. Deficiency of calcium, magnesium, or phosphorus may also cause rickets. It predominantly affects children who suffer from severe malnutrition. It manifests with bone pain, fractures, muscle weakness, and skeletal deformities.
• Disease Hierarchy:
  DIS90YV3: Bone remodeling disease
  DISH89YF: Rickets
• ICD Code:
  ICD-11: ICD-11: 5B57
  ICD-10: ICD-10: E55, E55.9
  Expand ICD-11: '5B57
  Expand ICD-10: 'E55; 'E55.9
• Disease Identifiers:
  MONDO ID: MONDO_0005520
  MESH ID: D012279
  UMLS CUI: C0035579
  MedGen ID: 48470
  HPO ID: HP:0002748
  SNOMED CT ID: 41345002

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 5 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Calcidiol	DMN4CV5	Approved	Small molecular drug	[1]
Calcitriol	DM8ZVJ7	Approved	Small molecular drug	[2]
Cholecalciferol	DMGU74E	Approved	Small molecular drug	[3]
Dihydrotachysterol	DMFB97P	Approved	Small molecular drug	[4]
Ergocalciferol	DMHO0AR	Approved	Small molecular drug	[5]

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
Seocalcitol	DMKL9QO	Phase 3	Small molecular drug	[6]

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
ALPL	TTMR5UV	Strong	Biomarker	[7]
FGF23	TT2IZ4K	Strong	Altered Expression	[8]
PTH	TT6F7GZ	Strong	Altered Expression	[9]
MMP13	TTHY57M	Definitive	Biomarker	[10]
PTH1R	TTFPD47	Definitive	Biomarker	[11]

This Disease Is Related to 3 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC20A2	DTFD4VB	Strong	Genetic Variation	[12]
SLC34A1	DT42EWA	Strong	Genetic Variation	[13]
SLC34A3	DTKS517	Strong	Genetic Variation	[14]

This Disease Is Related to 4 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CYP27B1	DE3FYEM	moderate	Biomarker	[15]
DHCR7	DEL7GFA	moderate	Biomarker	[16]
NADSYN1	DELF8BA	moderate	Biomarker	[16]
CYP2R1	DEBIHM3	Strong	Genetic Variation	[17]

This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
TALDO1	OTDKV2S2	moderate	Biomarker	[18]
BGLAP	OTK1YLWQ	Strong	Altered Expression	[19]
CLCN5	OT9YXZSO	Strong	Biomarker	[20]
CLDN16	OTTHAIKR	Strong	Genetic Variation	[13]
DMP1	OTBWBWW7	Strong	Biomarker	[21]
FAM20C	OTW5YZ7X	Strong	Genetic Variation	[22]

References

• [1] Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and biochemical effects on bone and mineral metabolism of daily and weekly dosage regimens. Osteoporos Int. 2017 Nov;28(11):3239-3249.
• [2] Calcitriol FDA Label
• [3] Cholecalciferol FDA Label
• [4] End-organ resistance to 1,25-dihydroxycholecalciferol. Lancet. 1980 Mar 8;1(8167):504-6.
• [5] Ergocalciferol FDA Label
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2777).
• [7] Enzyme replacement therapy prevents dental defects in a model of hypophosphatasia.J Dent Res. 2011 Apr;90(4):470-6. doi: 10.1177/0022034510393517. Epub 2011 Jan 6.
• [8] Tumor-induced osteomalacia: experience from three tertiary care centers in India.Endocr Connect. 2019 Mar;8(3):266-276. doi: 10.1530/EC-18-0552.
• [9] Calciotropic Hormones and the Prevalence of Vertebral Fractures in Chinese Postmenopausal Women with Vitamin D Insufficiency: Peking Vertebral Fracture Study.Calcif Tissue Int. 2019 Jun;104(6):622-630. doi: 10.1007/s00223-019-00531-2. Epub 2019 Feb 8.
• [10] Gene expression of matrix metalloproteinase 9 (MMP9), matrix metalloproteinase 13 (MMP13), vascular endothelial growth factor (VEGF) and fibroblast growth factor 23 (FGF23) in femur and vertebra tissues of the hypovitaminosis D kyphotic pig model.Br J Nutr. 2018 Aug;120(4):404-414. doi: 10.1017/S0007114518001605. Epub 2018 Jul 11.
• [11] Parathyroid receptor gene expression by epiphyseal growth plates in rickets and tibial dyschondroplasia.Mol Cell Endocrinol. 1999 Mar 25;149(1-2):185-95. doi: 10.1016/s0303-7207(98)00231-7.
• [12] First report of a de novo mutation at SLC20A2 in a patient with brain calcification.J Mol Neurosci. 2014 Dec;54(4):748-51. doi: 10.1007/s12031-014-0357-9. Epub 2014 Jun 27.
• [13] Genetic causes of hypercalciuric nephrolithiasis.Pediatr Nephrol. 2009 Dec;24(12):2321-32. doi: 10.1007/s00467-008-0807-0. Epub 2008 Apr 30.
• [14] Analysis of opossum kidney NaPi-IIc sodium-dependent phosphate transporter to understand Pi handling in human kidney.Clin Exp Nephrol. 2019 Mar;23(3):313-324. doi: 10.1007/s10157-018-1653-4. Epub 2018 Oct 13.
• [15] Absence of Calcitriol Causes Increased Lactational Bone Loss and Lower Milk Calcium but Does Not Impair Post-lactation Bone Recovery in Cyp27b1 Null Mice.J Bone Miner Res. 2018 Jan;33(1):16-26. doi: 10.1002/jbmr.3217. Epub 2017 Aug 2.
• [16] Relationship between polymorphisms in vitamin D metabolism-related genes and the risk of rickets in Han Chinese children.BMC Med Genet. 2013 Sep 30;14:101. doi: 10.1186/1471-2350-14-101.
• [17] CYP2R1 mutations causing vitamin D-deficiency rickets.J Steroid Biochem Mol Biol. 2017 Oct;173:333-336. doi: 10.1016/j.jsbmb.2016.07.014. Epub 2016 Jul 27.
• [18] Transaldolase deficiency in a two-year-old boy with cirrhosis.Mol Genet Metab. 2008 Jun;94(2):255-8. doi: 10.1016/j.ymgme.2008.01.011. Epub 2008 Mar 10.
• [19] Vitamin D Deficiency Is Associated with Increased Osteocalcin Levels in Acute Aortic Dissection: A Pilot Study on Elderly Patients.Mediators Inflamm. 2017;2017:6412531. doi: 10.1155/2017/6412531. Epub 2017 Jul 2.
• [20] Dent Disease in Chinese Children and Findings from Heterozygous Mothers: Phenotypic Heterogeneity, Fetal Growth, and 10 Novel Mutations.J Pediatr. 2016 Jul;174:204-210.e1. doi: 10.1016/j.jpeds.2016.04.007. Epub 2016 May 9.
• [21] The rachitic tooth.Endocr Rev. 2014 Feb;35(1):1-34. doi: 10.1210/er.2013-1009. Epub 2013 Dec 4.
• [22] Hereditary hypophosphatemia in Norway: a retrospective population-based study of genotypes, phenotypes, and treatment complications.Eur J Endocrinol. 2016 Feb;174(2):125-36. doi: 10.1530/EJE-15-0515. Epub 2015 Nov 5.