Details of Disease

General Information of Disease (ID: DISICS0V)

• Disease Name: Hypoparathyroidism
• Synonyms: parathyroid, underactivity of; hypoparathyroidism, idiopathic (subtype)
• Disease Class: 5A50: Hypo-parathyroidism
• Definition: Hypoparathyroidism is is an endocrine disorder in which the parathyroid glands in the neck do not produce enough parathyroid hormone (PTH). Common signs and symptoms includeabdominal pain, brittle nails, cataracts, dry hair and skin,muscle cramps,tetany, pain in the face, legs, and feet, seizures, tingling sensation,and weakened tooth enamel (in children). It may be caused byinjury to the parathyroid glands (e.g., during surgery). Other causes, include low blood magnesium levels, a side effect of radioactive iodine treatment for hyperthyroidism, metabolic alkalosis, DiGeorge syndrome, and type I polyglandular autoimmune syndrome. The goal of treatment is to restore the calcium and mineral balance in the body.
• Disease Hierarchy:
  DISJKZDC: Parathyroid disease
  DISICS0V: Hypoparathyroidism
• ICD Code:
  ICD-11: ICD-11: 5A50
  ICD-9: ICD-9: 252.1
  Expand ICD-11: '5A50
  Expand ICD-10: 'E20; 'E20.8; 'E20.9
  Expand ICD-9: 252.1
• Disease Identifiers:
  MONDO ID: MONDO_0001220
  MESH ID: D007011
  UMLS CUI: C0020626
  MedGen ID: 6985
  HPO ID: HP:0000829
  SNOMED CT ID: 36976004

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
Calcitriol	DM8ZVJ7	Approved	Small molecular drug	[1]
Cholecalciferol	DMGU74E	Approved	Small molecular drug	[2]
Dihydrotachysterol	DMFB97P	Approved	Small molecular drug	[3]
Ergocalciferol	DMHO0AR	Approved	Small molecular drug	[4]
Alfacalcidol	DM1237M	Phase 4	NA	[5]

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
PCO371	DMNHSI8	Phase 1	NA	[6]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ADH1A	TT5AHZ0	Strong	Genetic Variation	[7]
FGF23	TT2IZ4K	Strong	Altered Expression	[8]
GATA3	TT45KOB	Strong	Genetic Variation	[9]
GNA11	TTSRXJW	Strong	Biomarker	[10]
PTH1R	TTFPD47	Strong	Biomarker	[11]
TRPM6	TTV76RD	Strong	Genetic Variation	[12]

This Disease Is Related to 20 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GCM2	OTSKNPTI	Limited	Biomarker	[13]
PTMS	OT9PS4Q0	Limited	Biomarker	[14]
TBX1	OTQLBPRA	Disputed	Genetic Variation	[15]
AIRE	OTA7G1Y1	moderate	Genetic Variation	[16]
FAM111A	OTVLARLG	moderate	Genetic Variation	[17]
PTRH1	OTOAOS93	moderate	Biomarker	[18]
AP2S1	OTEV2XGW	Strong	Genetic Variation	[19]
ASAH1	OT1DNGXL	Strong	Biomarker	[20]
CLDN14	OTS7GKOI	Strong	Biomarker	[21]
CORO7	OTG7MEAJ	Strong	Biomarker	[22]
DGCR2	OTEGL17Z	Strong	Genetic Variation	[23]
HADHB	OT4Y1I62	Strong	Genetic Variation	[24]
NLRP5	OTLU1YML	Strong	Biomarker	[25]
NUDT11	OTFDXJA1	Strong	Genetic Variation	[26]
PHPT1	OTFYWNFX	Strong	Biomarker	[20]
TBCE	OTGBSTKS	Strong	Biomarker	[12]
DIAPH2	OTBEYFEZ	Definitive	Biomarker	[27]
POF1B	OTFWNK8G	Definitive	Biomarker	[27]
QRSL1	OTJDU2UG	Definitive	Genetic Variation	[28]
SOX3	OT1CRCOB	Definitive	Biomarker	[20]

References

• [1] Calcitriol FDA Label
• [2] Cholecalciferol FDA Label
• [3] Hypoparathyroidism and pseudo-hypoparathyroidism. Br Med J. 1954 Apr 17;1(4867):903-9.
• [4] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 040833.
• [5] Auditing the Efficacy and Safety of Alfacalcidol and Calcium Therapy in Idiopathic Hypoparathyroidism. J Clin Endocrinol Metab. 2019 Apr 1;104(4):1325-1335.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Treatment of Autosomal Dominant Hypocalcemia Type 1 With the Calcilytic NPSP795 (SHP635).J Bone Miner Res. 2019 Sep;34(9):1609-1618. doi: 10.1002/jbmr.3747. Epub 2019 Jul 26.
• [8] Under-recognized Hypoparathyroidism in Thalassemia.J Clin Res Pediatr Endocrinol. 2018 Nov 29;10(4):324-330. doi: 10.4274/jcrpe.0020. Epub 2018 May 4.
• [9] A rare case of deafness and renal abnormalities in HDR syndrome caused by a de novo mutation in the GATA3 gene.Genet Mol Biol. 2018 Oct-Dec;41(4):794-798. doi: 10.1590/1678-4685-GMB-2017-0194. Epub 2018 Nov 14.
• [10] Diseases associated with calcium-sensing receptor.Orphanet J Rare Dis. 2017 Jan 25;12(1):19. doi: 10.1186/s13023-017-0570-z.
• [11] Structure and dynamics of the active human parathyroid hormone receptor-1.Science. 2019 Apr 12;364(6436):148-153. doi: 10.1126/science.aav7942.
• [12] Comprehensive next-generation sequencing analyses of hypoparathyroidism: identification of novel GCM2 mutations.J Clin Endocrinol Metab. 2014 Nov;99(11):E2421-8. doi: 10.1210/jc.2014-2174. Epub 2014 Aug 19.
• [13] Idiopathic hypoparathyroidism with extensive intracranial calcification in children: First report from Saudi Arabia.Medicine (Baltimore). 2017 Apr;96(16):e6347. doi: 10.1097/MD.0000000000006347.
• [14] MANAGEMENT OF ENDOCRINE DISEASE: Unmet therapeutic, educational and scientific needs in parathyroid disorders.Eur J Endocrinol. 2019 Sep 1;181(3):P1-P19. doi: 10.1530/EJE-19-0316. Epub 2019 Jun 1.
• [15] Heterozygous Mutations in TBX1 as a Cause of Isolated Hypoparathyroidism.J Clin Endocrinol Metab. 2018 Nov 1;103(11):4023-4032. doi: 10.1210/jc.2018-01260.
• [16] Exome Sequencing Reveals Mutations in AIRE as a Cause of Isolated Hypoparathyroidism. J Clin Endocrinol Metab. 2017 May 1;102(5):1726-1733. doi: 10.1210/jc.2016-3836.
• [17] FAM111A mutations result in hypoparathyroidism and impaired skeletal development. Am J Hum Genet. 2013 Jun 6;92(6):990-5. doi: 10.1016/j.ajhg.2013.04.020. Epub 2013 May 16.
• [18] Advances in the treatment of hypoparathyroidism with PTH 1-34.Bone. 2019 Mar;120:535-541. doi: 10.1016/j.bone.2018.09.018. Epub 2018 Sep 21.
• [19] Analysis of AP2S1, a calcium-sensing receptor regulator, in familial and sporadic isolated hypoparathyroidism.J Clin Endocrinol Metab. 2014 Mar;99(3):E469-73. doi: 10.1210/jc.2013-3136. Epub 2014 Jan 1.
• [20] Bone Mineral Density and Its Serial Changes Are Associated With PTH Levels in Pseudohypoparathyroidism Type 1B Patients.J Bone Miner Res. 2018 Apr;33(4):743-752. doi: 10.1002/jbmr.3360. Epub 2018 Jan 3.
• [21] Parathyroid hormone controls paracellular Ca(2+) transport in the thick ascending limb by regulating the tight-junction protein Claudin14.Proc Natl Acad Sci U S A. 2017 Apr 18;114(16):E3344-E3353. doi: 10.1073/pnas.1616733114. Epub 2017 Apr 3.
• [22] Primary hyperparathyroidism: Dynamic postoperative metabolic changes.Clin Endocrinol (Oxf). 2018 Jan;88(1):129-138. doi: 10.1111/cen.13476. Epub 2017 Oct 1.
• [23] Expression and mutation analysis of BRUNOL3, a candidate gene for heart and thymus developmental defects associated with partial monosomy 10p.J Mol Med (Berl). 2002 Jul;80(7):431-42. doi: 10.1007/s00109-002-0331-9. Epub 2002 Apr 4.
• [24] Mutations in HADHB, which encodes the -subunit of mitochondrial trifunctional protein, cause infantile onset hypoparathyroidism and peripheral polyneuropathy.Am J Med Genet A. 2014 May;164A(5):1180-7. doi: 10.1002/ajmg.a.36434. Epub 2014 Mar 24.
• [25] Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen.N Engl J Med. 2008 Mar 6;358(10):1018-28. doi: 10.1056/NEJMoa0706487.
• [26] A new mutation site in the AIRE gene causes autoimmune polyendocrine syndrome type 1.Immunogenetics. 2017 Oct;69(10):643-651. doi: 10.1007/s00251-017-0995-5. Epub 2017 May 24.
• [27] Autoimmune endocrine diseases.Minerva Endocrinol. 2018 Sep;43(3):305-322. doi: 10.23736/S0391-1977.17.02757-2. Epub 2017 Oct 9.
• [28] The syndrome of hypoparathyroidism, deafness, and renal anomalies.Endocr Pract. 2013 Nov-Dec;19(6):1035-42. doi: 10.4158/EP13050.RA.