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Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis

MedGen UID:
1843047
•Concept ID:
C5679977
•
Disease or Syndrome
Synonyms: familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis; FHHNC; Michellis-Castrillo syndrome; Primary hypomagnesemia with hypercalciuria and nephrocalcinosis
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Monarch Initiative: MONDO:0017624
Orphanet: ORPHA306516

Definition

Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a form of familial primary hypomagnesemia (FPH, see this term), characterized by renal magnesium (Mg) and calcium (Ca) wasting, nephrocalcinosis, kidney failure and, in some cases, severe ocular impairment. Two subtypes of FHHNC are described: FHHNC with severe ocular involvement (FHHNCOI) and without severe ocular involvement (FHHN) (see these terms). [from ORDO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFamilial primary hypomagnesemia with hypercalciuria and nephrocalcinosis

Professional guidelines

PubMed

RenalTube: a network tool for clinical and genetic diagnosis of primary tubulopathies.
Mejía N, Santos F, Claverie-Martín F, García-Nieto V, Ariceta G, Castaño L; RenalTube group
Eur J Pediatr 2013 Jun;172(6):775-80. Epub 2013 Feb 7 doi: 10.1007/s00431-013-1934-6. PMID: 23389821
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: phenotype-genotype correlation and outcome in 32 patients with CLDN16 or CLDN19 mutations.
Godron A, Harambat J, Boccio V, Mensire A, May A, Rigothier C, Couzi L, Barrou B, Godin M, Chauveau D, Faguer S, Vallet M, Cochat P, Eckart P, Guest G, Guigonis V, Houillier P, Blanchard A, Jeunemaitre X, Vargas-Poussou R
Clin J Am Soc Nephrol 2012 May;7(5):801-9. Epub 2012 Mar 15 doi: 10.2215/CJN.12841211. PMID: 22422540Free PMC Article

Recent clinical studies

Etiology

Living kidney donation from people at risk of nephrolithiasis, with a focus on the genetic forms.
Gambaro G, Zaza G, Citterio F, Naticchia A, Ferraro PM
Urolithiasis 2019 Feb;47(1):115-123. Epub 2018 Nov 23 doi: 10.1007/s00240-018-1092-4. PMID: 30470867
Genetic causes of hypomagnesemia, a clinical overview.
Viering DHHM, de Baaij JHF, Walsh SB, Kleta R, Bockenhauer D
Pediatr Nephrol 2017 Jul;32(7):1123-1135. Epub 2016 May 27 doi: 10.1007/s00467-016-3416-3. PMID: 27234911Free PMC Article
Mechanisms and causes of hypomagnesemia.
Agus ZS
Curr Opin Nephrol Hypertens 2016 Jul;25(4):301-7. doi: 10.1097/MNH.0000000000000238. PMID: 27219040
Claudins and mineral metabolism.
Hou J
Curr Opin Nephrol Hypertens 2016 Jul;25(4):308-13. doi: 10.1097/MNH.0000000000000239. PMID: 27191348Free PMC Article
Hereditary causes of kidney stones and chronic kidney disease.
Edvardsson VO, Goldfarb DS, Lieske JC, Beara-Lasic L, Anglani F, Milliner DS, Palsson R
Pediatr Nephrol 2013 Oct;28(10):1923-42. Epub 2013 Jan 20 doi: 10.1007/s00467-012-2329-z. PMID: 23334384Free PMC Article

Diagnosis

Research progress on renal calculus associate with inborn error of metabolism.
Song Y, Zhao C, Li D
Zhejiang Da Xue Xue Bao Yi Xue Ban 2023 Apr 25;52(2):169-177. doi: 10.3724/zdxbyxb-2022-0698. PMID: 37283101Free PMC Article
mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and Cardiomyopathy.
Schlingmann KP, Jouret F, Shen K, Nigam A, Arjona FJ, Dafinger C, Houillier P, Jones DP, Kleinerüschkamp F, Oh J, Godefroid N, Eltan M, Güran T, Burtey S, Parotte MC, König J, Braun A, Bos C, Ibars Serra M, Rehmann H, Zwartkruis FJT, Renkema KY, Klingel K, Schulze-Bahr E, Schermer B, Bergmann C, Altmüller J, Thiele H, Beck BB, Dahan K, Sabatini D, Liebau MC, Vargas-Poussou R, Knoers NVAM, Konrad M, de Baaij JHF
J Am Soc Nephrol 2021 Nov;32(11):2885-2899. Epub 2021 Oct 4 doi: 10.1681/ASN.2021030333. PMID: 34607910Free PMC Article
Nephrolithiasis and Nephrocalcinosis in Children - Metabolic and Genetic Factors.
Tasic V, Gucev Z
Pediatr Endocrinol Rev 2015 Sep;13(1):468-76. PMID: 26540764
Hypomagnesaemia-hypercalciuria-nephrocalcinosis: a report of nine cases and a review.
Benigno V, Canonica CS, Bettinelli A, von Vigier RO, Truttmann AC, Bianchetti MG
Nephrol Dial Transplant 2000 May;15(5):605-10. doi: 10.1093/ndt/15.5.605. PMID: 10809799
Magnesium metabolism in childhood.
Geven WB, Monnens LA, Willems JL
Miner Electrolyte Metab 1993;19(4-5):308-13. PMID: 8264518

Therapy

Genetic causes of hypomagnesemia, a clinical overview.
Viering DHHM, de Baaij JHF, Walsh SB, Kleta R, Bockenhauer D
Pediatr Nephrol 2017 Jul;32(7):1123-1135. Epub 2016 May 27 doi: 10.1007/s00467-016-3416-3. PMID: 27234911Free PMC Article
Mechanisms and causes of hypomagnesemia.
Agus ZS
Curr Opin Nephrol Hypertens 2016 Jul;25(4):301-7. doi: 10.1097/MNH.0000000000000238. PMID: 27219040
Proton pump inhibitors and hospitalization with hypomagnesemia: a population-based case-control study.
Zipursky J, Macdonald EM, Hollands S, Gomes T, Mamdani MM, Paterson JM, Lathia N, Juurlink DN
PLoS Med 2014 Sep;11(9):e1001736. Epub 2014 Sep 30 doi: 10.1371/journal.pmed.1001736. PMID: 25268962Free PMC Article
A novel CLDN16 mutation in a large family with familial hypomagnesaemia with hypercalciuria and nephrocalcinosis.
Deeb A, Abood SA, Simon J, Dastoor H, Pearce SH, Sayer JA
BMC Res Notes 2013 Dec 10;6:527. doi: 10.1186/1756-0500-6-527. PMID: 24321194Free PMC Article
Primary familial hypomagnesemia syndrome: a new approach in treatment.
Nesibe A, Sinasi O
J Pediatr Endocrinol Metab 2012;25(5-6):599-602. PMID: 22876566

Prognosis

Characterization of two novel mutations in the claudin-16 and claudin-19 genes that cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
Perdomo-Ramirez A, Aguirre M, Davitaia T, Ariceta G, Ramos-Trujillo E; RenalTube Group, Claverie-Martin F
Gene 2019 Mar 20;689:227-234. Epub 2018 Dec 18 doi: 10.1016/j.gene.2018.12.024. PMID: 30576809
Hereditary causes of kidney stones and chronic kidney disease.
Edvardsson VO, Goldfarb DS, Lieske JC, Beara-Lasic L, Anglani F, Milliner DS, Palsson R
Pediatr Nephrol 2013 Oct;28(10):1923-42. Epub 2013 Jan 20 doi: 10.1007/s00467-012-2329-z. PMID: 23334384Free PMC Article
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
Kari JA, Farouq M, Alshaya HO
Pediatr Nephrol 2003 Jun;18(6):506-10. Epub 2003 Apr 29 doi: 10.1007/s00467-003-1139-8. PMID: 12720080
Hypomagnesaemia-hypercalciuria-nephrocalcinosis: a report of nine cases and a review.
Benigno V, Canonica CS, Bettinelli A, von Vigier RO, Truttmann AC, Bianchetti MG
Nephrol Dial Transplant 2000 May;15(5):605-10. doi: 10.1093/ndt/15.5.605. PMID: 10809799
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
Praga M, Vara J, González-Parra E, Andrés A, Alamo C, Araque A, Ortiz A, Rodicio JL
Kidney Int 1995 May;47(5):1419-25. doi: 10.1038/ki.1995.199. PMID: 7637271

Clinical prediction guides

Etiological Profile of Nephrocalcinosis in Children from Southern India.
Ramya K, Krishnamurthy S, Sivamurukan P
Indian Pediatr 2020 May 15;57(5):415-419. Epub 2020 Mar 12 PMID: 32221050
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: phenotype-genotype correlation and outcome in 32 patients with CLDN16 or CLDN19 mutations.
Godron A, Harambat J, Boccio V, Mensire A, May A, Rigothier C, Couzi L, Barrou B, Godin M, Chauveau D, Faguer S, Vallet M, Cochat P, Eckart P, Guest G, Guigonis V, Houillier P, Blanchard A, Jeunemaitre X, Vargas-Poussou R
Clin J Am Soc Nephrol 2012 May;7(5):801-9. Epub 2012 Mar 15 doi: 10.2215/CJN.12841211. PMID: 22422540Free PMC Article
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
Kari JA, Farouq M, Alshaya HO
Pediatr Nephrol 2003 Jun;18(6):506-10. Epub 2003 Apr 29 doi: 10.1007/s00467-003-1139-8. PMID: 12720080
Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene.
Weber S, Hoffmann K, Jeck N, Saar K, Boeswald M, Kuwertz-Broeking E, Meij II, Knoers NV, Cochat P, Suláková T, Bonzel KE, Soergel M, Manz F, Schaerer K, Seyberth HW, Reis A, Konrad M
Eur J Hum Genet 2000 Jun;8(6):414-22. doi: 10.1038/sj.ejhg.5200475. PMID: 10878661
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
Praga M, Vara J, González-Parra E, Andrés A, Alamo C, Araque A, Ortiz A, Rodicio JL
Kidney Int 1995 May;47(5):1419-25. doi: 10.1038/ki.1995.199. PMID: 7637271

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