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Intestinal hypomagnesemia 1(HOMG1; HSH)

MedGen UID:
355596
Concept ID:
C1865974
Disease or Syndrome
Synonyms: Hypomagnesemia with Secondary Hypocalcemia; HYPOMAGNESEMIA, INTESTINAL, WITH SECONDARY HYPOCALCEMIA; HYPOMAGNESEMIC TETANY
SNOMED CT: Hypomagnesemia with secondary hypocalcemia (711151004); Intestinal hypomagnesemia 1 (711151004); Intestinal hypomagnesemia with secondary hypocalcemia (711151004); Familial primary hypomagnesemia with hypocalcuria (711151004)
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).
 
Gene (location): TRPM6 (9q21.13)
 
Monarch Initiative: MONDO:0011176
OMIM®: 602014
Orphanet: ORPHA30924

Definition

Familial hypomagnesemia with secondary hypocalcemia (HOMG1) is a rare autosomal recessive disorder characterized by very low serum magnesium levels. Hypocalcemia is a secondary consequence of parathyroid failure and parathyroid hormone resistance as a result of severe magnesium deficiency. The disease typically manifests during the first months of life with generalized convulsions or signs of increased neuromuscular excitability, such as muscle spasms or tetany. Untreated, the disease may be fatal or lead to severe neurologic damage. Treatment includes immediate administration of magnesium, usually intravenously, followed by life-long high-dose oral magnesium (review by Knoers, 2009). Genetic Heterogeneity of Hypomagnesemia A form of hypomagnesemia due to kidney defects and high urinary magnesium excretion associated with hypocalciuria (HOMG2; 154020) is caused by mutation in the FXYD2 gene (601814). Renal hypomagnesemia-3 (HOMG3; 248250), associated with hypercalciuria and nephrocalcinosis, is caused by mutation in the CLDN16 gene (603959). Renal hypomagnesemia-4 (HOMG4; 611718), which is normocalciuric, is caused by mutation in the EGF gene (131530). Renal hypomagnesemia-5 with or without ocular involvement (HOMG5; 248190), associated with hypercalciuria and nephrocalcinosis, is caused by mutation in the CLDN19 gene (610036). Renal hypomagnesemia-6 (HOMG6; 613882) is caused by mutation in the CNNM2 gene (607803). Renal hypomagnesemia-7 with or without dilated cardiomyopathy (HOMG7; 620152) is caused by mutation in the RRAGD gene (608268). Patients with Gitelman syndrome (263800) and Bartter syndrome (see 241200) also show hypomagnesemia, and steatorrhea and severe chronic diarrhea states, such as Crohn disease (see 226600) and Whipple disease, that can result in severe hypomagnesemia. [from OMIM]

Additional description

From MedlinePlus Genetics
Hypomagnesemia with secondary hypocalcemia is an inherited condition caused by the body's inability to absorb and retain magnesium that is taken in through the diet. As a result, magnesium levels in the blood are severely low (hypomagnesemia).

Hypomagnesemia impairs the function of the parathyroid glands, which are small hormone-producing glands located in the neck. Normally, the parathyroid glands release a hormone that increases blood calcium levels when they are low. Magnesium is required for the production and release of parathyroid hormone, so when magnesium is too low, insufficient parathyroid hormone is produced and blood calcium levels are also reduced (hypocalcemia). The hypocalcemia is described as "secondary" because it occurs as a consequence of hypomagnesemia.

Shortages of magnesium and calcium can cause neurological problems that begin in infancy, including painful muscle spasms (tetany) and seizures. If left untreated, hypomagnesemia with secondary hypocalcemia can lead to developmental delay, intellectual disability, a failure to gain weight and grow at the expected rate (failure to thrive), and heart failure.  https://medlineplus.gov/genetics/condition/hypomagnesemia-with-secondary-hypocalcemia

Clinical features

From HPO
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Muscle spasm
MedGen UID:
52431
Concept ID:
C0037763
Sign or Symptom
Sudden and involuntary contractions of one or more muscles.
Tetany
MedGen UID:
11748
Concept ID:
C0039621
Finding
A condition characterized by intermittent involuntary contraction of muscles (spasms) related to hypocalcemia or occasionally magnesium deficiency.
Hypocalcemia
MedGen UID:
5705
Concept ID:
C0020598
Disease or Syndrome
An abnormally decreased calcium concentration in the blood.
Hypomagnesemia
MedGen UID:
57481
Concept ID:
C0151723
Disease or Syndrome
An abnormally decreased magnesium concentration in the blood.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVIntestinal hypomagnesemia 1

Professional guidelines

PubMed

Au WY, Kwong YL
Acta Pharmacol Sin 2008 Mar;29(3):296-304. doi: 10.1111/j.1745-7254.2008.00771.x. PMID: 18298894
Frazier TG, Mucha ME, Rush IH, Trull EJ, Carlson SA, O'Connor JA
J Surg Oncol 1980;13(1):35-8. doi: 10.1002/jso.2930130106. PMID: 6766197
Tsang RC, Steichen JJ, Chan GM
Crit Care Med 1977 Jan-Feb;5(1):56-61. PMID: 837701

Recent clinical studies

Etiology

Agus ZS
Curr Opin Nephrol Hypertens 2016 Jul;25(4):301-7. doi: 10.1097/MNH.0000000000000238. PMID: 27219040
Cools E, Missant C
Acta Anaesthesiol Belg 2014;65(1):1-8. PMID: 24988822
Drug Ther Bull 2013 Mar;51(3):33-6. doi: 10.1136/dtb.2013.1.0169. PMID: 23482516
Tapia J, Murguia R, Garcia G, de los Monteros PE, Oñate E
World J Surg 1999 Jun;23(6):596-602. doi: 10.1007/pl00012353. PMID: 10227930
Fillastre JP, Raguenez-Viotte G
Toxicol Lett 1989 Mar;46(1-3):163-75. doi: 10.1016/0378-4274(89)90125-2. PMID: 2650023

Diagnosis

Zhao C, Lin Y, Jiang Z
Clin Lab 2023 Oct 1;69(10) doi: 10.7754/Clin.Lab.2023.230505. PMID: 37844054
Bockenhauer D, Jaureguiberry G
Pediatr Nephrol 2016 May;31(5):707-14. Epub 2015 Jul 8 doi: 10.1007/s00467-015-3142-2. PMID: 26160100
Cools E, Missant C
Acta Anaesthesiol Belg 2014;65(1):1-8. PMID: 24988822
Corleto VD, Festa S, Di Giulio E, Annibale B
Curr Opin Endocrinol Diabetes Obes 2014 Feb;21(1):3-8. doi: 10.1097/MED.0000000000000031. PMID: 24310148
Lameris AL, Monnens LA, Bindels RJ, Hoenderop JG
Clin Sci (Lond) 2012 Jul;123(1):1-14. doi: 10.1042/CS20120045. PMID: 22409531

Therapy

Agus ZS
Curr Opin Nephrol Hypertens 2016 Jul;25(4):301-7. doi: 10.1097/MNH.0000000000000238. PMID: 27219040
de Baaij JH, Hoenderop JG, Bindels RJ
Physiol Rev 2015 Jan;95(1):1-46. doi: 10.1152/physrev.00012.2014. PMID: 25540137
Drug Ther Bull 2013 Mar;51(3):33-6. doi: 10.1136/dtb.2013.1.0169. PMID: 23482516
Tapia J, Murguia R, Garcia G, de los Monteros PE, Oñate E
World J Surg 1999 Jun;23(6):596-602. doi: 10.1007/pl00012353. PMID: 10227930
Fillastre JP, Raguenez-Viotte G
Toxicol Lett 1989 Mar;46(1-3):163-75. doi: 10.1016/0378-4274(89)90125-2. PMID: 2650023

Prognosis

Garcia-Nieto VM, Claverie-Martin F, Moraleda-Mesa T, Perdomo-Ramírez A, Fraga-Rodríguez GM, Luis-Yanes MI, Ramos-Trujillo E; Grupo RenalTube
Nefrologia (Engl Ed) 2024 Jan-Feb;44(1):23-31. Epub 2024 Feb 12 doi: 10.1016/j.nefroe.2024.02.003. PMID: 38350738
Bayramoğlu E, Keskin M, Aycan Z, Savaş-Erdeve Ş, Çetinkaya S
J Clin Res Pediatr Endocrinol 2021 Aug 23;13(3):300-307. Epub 2021 Feb 10 doi: 10.4274/jcrpe.galenos.2021.2020.0192. PMID: 33565749Free PMC Article
Bockenhauer D, Jaureguiberry G
Pediatr Nephrol 2016 May;31(5):707-14. Epub 2015 Jul 8 doi: 10.1007/s00467-015-3142-2. PMID: 26160100
Zhao Z, Pei Y, Huang X, Liu Y, Yang W, Sun J, Si N, Xing X, Li M, Wang O, Jiang Y, Zhang X, Xia W
Am J Nephrol 2013;37(6):541-8. Epub 2013 May 16 doi: 10.1159/000350886. PMID: 23689795
Meij IC, Koenderink JB, De Jong JC, De Pont JJ, Monnens LA, Van Den Heuvel LP, Knoers NV
Ann N Y Acad Sci 2003 Apr;986:437-43. doi: 10.1111/j.1749-6632.2003.tb07226.x. PMID: 12763862

Clinical prediction guides

Garcia-Nieto VM, Claverie-Martin F, Moraleda-Mesa T, Perdomo-Ramírez A, Fraga-Rodríguez GM, Luis-Yanes MI, Ramos-Trujillo E; Grupo RenalTube
Nefrologia (Engl Ed) 2024 Jan-Feb;44(1):23-31. Epub 2024 Feb 12 doi: 10.1016/j.nefroe.2024.02.003. PMID: 38350738
Pruccoli J, Barbieri E, Visconti C, Pranzetti B, Pettenuzzo I, Moscano F, Malaspina E, Marino M, Valeriani B, Parmeggiani A
Eur J Pediatr 2024 Apr;183(4):1935-1941. Epub 2024 Feb 12 doi: 10.1007/s00431-024-05430-9. PMID: 38347260Free PMC Article
Pisani LF, Filippi E, Vavassori S, Munizio N, Vecchi M, Pastorelli L
Magnes Res 2016 Mar 1;29(1):1-10. doi: 10.1684/mrh.2016.0397. PMID: 27086964
Bockenhauer D, Jaureguiberry G
Pediatr Nephrol 2016 May;31(5):707-14. Epub 2015 Jul 8 doi: 10.1007/s00467-015-3142-2. PMID: 26160100
Fillastre JP, Raguenez-Viotte G
Toxicol Lett 1989 Mar;46(1-3):163-75. doi: 10.1016/0378-4274(89)90125-2. PMID: 2650023

Recent systematic reviews

Feng H, Zou L, Zhai X, Zhang S, Li J
BMC Gastroenterol 2022 May 15;22(1):246. doi: 10.1186/s12876-022-02318-6. PMID: 35570283Free PMC Article

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