Details of Disease

General Information of Disease (ID: DIS5ZVJP)

• Disease Name: Nephrocalcinosis
• Synonyms: hypercalcemic nephropathy
• Definition: Nephrocalcinosis is a disorder that occurs when too much calcium is deposited in the kidneys. It commonly occurs in premature infants. Individuals may not have symptoms or may have symptoms related to thecondition causing nephrocalcinosis. If kidney stones are present, symptoms may include blood in the urine, fever and chills, nausea and vomiting, and severe pain in the belly area, sides of the back (flank), groin, or testicles. Later symptoms may be associated with chronic kidney failure. It may be caused by use of certain medications or supplements, infection, or any condition that leads to high levels of calcium in the blood or urine including hyperparathyroidism, renal tubular acidosis, Alport syndrome, Bartter syndrome,and a variety of other conditions. Some of the underlying disorders that can cause nephrocalcinosis are genetic, with the inheritance pattern depending on the specific disorder. Treatment differs depending on the cause of nephrocalcinosis and often aims to prevent more calcium from being deposited in the kidneys.
• Disease Hierarchy:
  DISQP4OR: Calcinosis
  DISXWP4P: Nephropathy
  DIS5ZVJP: Nephrocalcinosis
• Disease Identifiers:
  MONDO ID: MONDO_0001567
  MESH ID: D009397
  UMLS CUI: C0027709
  MedGen ID: 10222
  HPO ID: HP:0000121
  SNOMED CT ID: 48638002

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 11 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CYP24A1	TT82UI1	Limited	Biomarker	[1]
SLC5A1	TT2UE56	moderate	Genetic Variation	[2]
TRPM6	TTV76RD	moderate	Biomarker	[3]
TRPV6	TTBK14N	moderate	Biomarker	[4]
AGXT	TTF5NVW	Strong	Genetic Variation	[5]
CASR	TTBUYHA	Strong	Genetic Variation	[6]
GATA3	TT45KOB	Strong	Genetic Variation	[7]
HNF4A	TT2F3CD	Strong	Genetic Variation	[8]
KCNJ1	TTJ13ST	Strong	Genetic Variation	[9]
SLC12A1	TTS087L	Strong	Genetic Variation	[5]
LRP2	TTPH1AJ	Definitive	Genetic Variation	[10]

This Disease Is Related to 5 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC26A1	DTJ785O	Limited	Biomarker	[11]
SLC34A1	DT42EWA	Strong	Biomarker	[1]
SLC34A3	DTKS517	Strong	Biomarker	[1]
SLC3A1	DTBCKVM	Strong	Genetic Variation	[5]
SLC4A1	DTB0Q3P	Strong	Genetic Variation	[12]

This Disease Is Related to 22 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CLDN19	OTVD6IBL	Limited	Genetic Variation	[13]
AP3B1	OTYTIH5Q	moderate	Biomarker	[14]
BSND	OTYWZWPD	moderate	Genetic Variation	[15]
CLDN10	OT2CVAKY	moderate	Biomarker	[16]
DCT	OTYVNTBG	moderate	Biomarker	[17]
FGL1	OTT0QHQ1	moderate	Biomarker	[14]
HPS1	OTKS5I7T	moderate	Biomarker	[14]
IHH	OT1DWGXC	moderate	Biomarker	[18]
LGI1	OTPS77HO	moderate	Genetic Variation	[19]
TNMD	OTHLVA9G	moderate	Biomarker	[20]
TRPV5	OTWF4L0U	moderate	Biomarker	[21]
AMMECR1	OTWMQ67T	Strong	Genetic Variation	[22]
ATP6V0A4	OT149Z7Q	Strong	Genetic Variation	[23]
ATP6V1B1	OT8FQ7MN	Strong	Genetic Variation	[23]
CLCN5	OT9YXZSO	Strong	Genetic Variation	[24]
CLPB	OT1I0IBK	Strong	Biomarker	[25]
FAM20A	OT5Z5IW8	Strong	Genetic Variation	[26]
GRHPR	OTLV63QV	Strong	Genetic Variation	[5]
OCRL	OTQ3L42N	Strong	Genetic Variation	[27]
PHEX	OTG7N3J7	Strong	Genetic Variation	[28]
MRGPRF	OT74OZ2Z	Definitive	Biomarker	[12]
RBFOX2	OTXY1WVH	Definitive	Biomarker	[12]

References

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• [2] Nephrocalcinosis in glucose-galactose malabsorption: nephrocalcinosis and proximal tubular dysfunction in a young infant with a novel mutation of SGLT1.Eur J Pediatr. 2008 Dec;167(12):1395-8. doi: 10.1007/s00431-008-0681-6. Epub 2008 Feb 21.
• [3] Clinical and molecular characterization of Turkish patients with familial hypomagnesaemia: novel mutations in TRPM6 and CLDN16 genes.Nephrol Dial Transplant. 2012 Feb;27(2):667-73. doi: 10.1093/ndt/gfr300. Epub 2011 Jun 9.
• [4] Two Cases of Mistaken Polyuria and Nephrocalcinosis in Infants with Glucose-Galactose Malabsorption: A Possible Role of 1,25(OH)2D3?,Fiscaletti M. Alos N
• [5] Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis andnephrocalcinosis.Kidney Int. 2018 Jan;93(1):204-213. doi: 10.1016/j.kint.2017.06.025. Epub 2017 Oct 12.
• [6] Pregnancy outcome in women with autosomal dominant hypocalcaemic hypercalciuric nephrocalcinosis.J Matern Fetal Neonatal Med. 2014 Nov;27(17):1826-8. doi: 10.3109/14767058.2013.879644. Epub 2014 Feb 10.
• [7] Renal phenotypic variability in HDR syndrome: glomerular nephropathy as a novel finding.Eur J Pediatr. 2013 Jan;172(1):107-10. doi: 10.1007/s00431-012-1845-y. Epub 2012 Oct 5.
• [8] Hnf4a deletion in the mouse kidney phenocopies Fanconi renotubular syndrome.JCI Insight. 2018 Jul 26;3(14):e97497. doi: 10.1172/jci.insight.97497. eCollection 2018 Jul 26.
• [9] Late-onset Bartter syndrome type II.Clin Kidney J. 2017 Oct;10(5):594-599. doi: 10.1093/ckj/sfx033. Epub 2017 May 8.
• [10] Hypercalciuria and nephrolithiasis: Expanding the renal phenotype of Donnai-Barrow syndrome.Clin Genet. 2018 Jul;94(1):187-188. doi: 10.1111/cge.13242. Epub 2018 Mar 13.
• [11] Urolithiasis and hepatotoxicity are linked to the anion transporter Sat1 in mice.J Clin Invest. 2010 Mar;120(3):706-12. doi: 10.1172/JCI31474. Epub 2010 Feb 15.
• [12] A novel SLC4A1 variant in an autosomal dominant distal renal tubular acidosis family with a severe phenotype.Endocrine. 2010 Jun;37(3):473-8. doi: 10.1007/s12020-010-9340-6. Epub 2010 Apr 17.
• [13] Characterization of two novel mutations in the claudin-16 and claudin-19 genes that cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis.Gene. 2019 Mar 20;689:227-234. doi: 10.1016/j.gene.2018.12.024. Epub 2018 Dec 18.
• [14] Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome.J Am Soc Nephrol. 2000 Aug;11(8):1449-1459. doi: 10.1681/ASN.V1181449.
• [15] Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome.Nephrol Dial Transplant. 2009 May;24(5):1455-64. doi: 10.1093/ndt/gfn689. Epub 2008 Dec 18.
• [16] Deletion of claudin-10 rescues claudin-16-deficient mice from hypomagnesemia and hypercalciuria.Kidney Int. 2018 Mar;93(3):580-588. doi: 10.1016/j.kint.2017.08.029. Epub 2017 Nov 10.
• [17] Bartter's and Gitelman's syndrome.Curr Opin Pediatr. 2017 Apr;29(2):179-186. doi: 10.1097/MOP.0000000000000447.
• [18] CYP24A1 Mutation in a Girl Infant with Idiopathic Infantile Hypercalcemia.J Clin Res Pediatr Endocrinol. 2018 Mar 1;10(1):83-86. doi: 10.4274/jcrpe.4841. Epub 2017 Sep 6.
• [19] Kidney volume, kidney function, and ambulatory blood pressure in children born extremely preterm with and without nephrocalcinosis.Pediatr Nephrol. 2019 Oct;34(10):1765-1776. doi: 10.1007/s00467-019-04293-9. Epub 2019 Jul 23.
• [20] Establishment of urinary exosome-like vesicles isolation protocol for FHHNC patients and evaluation of different exosomal RNA extraction methods.J Transl Med. 2018 Oct 11;16(1):278. doi: 10.1186/s12967-018-1651-z.
• [21] Urinary plasmin inhibits TRPV5 in nephrotic-range proteinuria.J Am Soc Nephrol. 2012 Nov;23(11):1824-34. doi: 10.1681/ASN.2011111126. Epub 2012 Sep 27.
• [22] X-linked elliptocytosis with impaired growth is related to mutated AMMECR1.Gene. 2017 Mar 30;606:47-52. doi: 10.1016/j.gene.2017.01.001. Epub 2017 Jan 9.
• [23] Pathophysiology, diagnosis and treatment of inherited distal renal tubular acidosis.J Nephrol. 2018 Aug;31(4):511-522. doi: 10.1007/s40620-017-0447-1. Epub 2017 Oct 9.
• [24] Phenotype and genotype of Dent's disease in three Korean boys.Pediatr Nephrol. 2005 Apr;20(4):455-9. doi: 10.1007/s00467-004-1769-5. Epub 2005 Feb 18.
• [25] Bi-allelic CLPB mutations cause cataract, renal cysts, nephrocalcinosis and 3-methylglutaconic aciduria, a novel disorder of mitochondrial protein disaggregation.J Inherit Metab Dis. 2015 Mar;38(2):211-9. doi: 10.1007/s10545-015-9813-0. Epub 2015 Jan 18.
• [26] Nephrocalcinosis in Amelogenesis Imperfecta Caused by the FAM20A Mutation.Nephron. 2018;139(2):189-196. doi: 10.1159/000486607. Epub 2018 Feb 13.
• [27] Renal phenotype in Lowe Syndrome: a selective proximal tubular dysfunction.Clin J Am Soc Nephrol. 2008 Sep;3(5):1430-6. doi: 10.2215/CJN.00520108. Epub 2008 May 14.
• [28] Hypophosphatemic Rickets.Pediatr Clin North Am. 2019 Feb;66(1):179-207. doi: 10.1016/j.pcl.2018.09.004.