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Primary hypomagnesemia(HOMG3)

MedGen UID:
120640
Concept ID:
C0268448
Disease or Syndrome
Synonyms: HOMG3; HYPOMAGNESEMIA 3, RENAL; Hypomagnesemia, familial, with hypercalciuria and nephrocalcinosis; Hypomagnesemia, isolated renal; HYPOMAGNESEMIA, PRIMARY, DUE TO DEFECT IN RENAL TUBULAR TRANSPORT OF MAGNESIUM; Magnesium, defect in renal tubular transport of
SNOMED CT: Primary hypomagnesemia (80710001)
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): CLDN16 (3q28)
 
Monarch Initiative: MONDO:0009550
OMIM®: 248250
Orphanet: ORPHA31043

Definition

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a progressive renal disorder characterized by excessive urinary Ca(2+) and Mg(2+) excretion. There is progressive loss of kidney function, and in about 50% of cases, the need for renal replacement therapy arises as early as the second decade of life (summary by Muller et al., 2006). Amelogenesis imperfecta may also be present in some patients (Bardet et al., 2016). A similar disorder with renal magnesium wasting, renal failure, and nephrocalcinosis (HOMG5; 248190) is caused by mutations in another tight-junction gene, CLDN19 (610036), and is distinguished by the association of severe ocular involvement. For a discussion of phenotypic and genetic heterogeneity of familial hypomagnesemia, see HOMG1 (602014). [from OMIM]

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
The presence of blood in the urine. Hematuria may be gross hematuria (visible to the naked eye) or microscopic hematuria (detected by dipstick or microscopic examination of the urine).
Hypercalciuria
MedGen UID:
43775
Concept ID:
C0020438
Finding
Abnormally high level of calcium in the urine.
Nephrocalcinosis
MedGen UID:
10222
Concept ID:
C0027709
Disease or Syndrome
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Polyuria
MedGen UID:
19404
Concept ID:
C0032617
Sign or Symptom
An increased rate of urine production.
Recurrent urinary tract infections
MedGen UID:
120466
Concept ID:
C0262655
Disease or Syndrome
Repeated infections of the urinary tract.
Nephrolithiasis
MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
The presence of calculi (stones) in the kidneys.
Chronic kidney disease
MedGen UID:
473458
Concept ID:
C1561643
Disease or Syndrome
Functional anomaly of the kidney persisting for at least three months.
Renal calcium wasting
MedGen UID:
392919
Concept ID:
C2673441
Finding
High urine calcium in the presence of hypocalcemia.
Hypermagnesiuria
MedGen UID:
392920
Concept ID:
C2673443
Finding
An increased concentration of magnesium the urine.
Hypocitraturia
MedGen UID:
392921
Concept ID:
C2673444
Finding
A lower than normal concentration of citrate(3-) in the urine.
Hypercitraturia
MedGen UID:
866741
Concept ID:
C4021090
Finding
A greater than normal concentration of citrate(3-) in the urine.
Renal magnesium wasting
MedGen UID:
1811452
Concept ID:
C5574944
Finding
High urine magnesium in the presence of hypomagnesemia.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
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.
Polydipsia
MedGen UID:
43214
Concept ID:
C0085602
Sign or Symptom
Excessive thirst manifested by excessive fluid intake.
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.
Hypomagnesemia
MedGen UID:
57481
Concept ID:
C0151723
Disease or Syndrome
An abnormally decreased magnesium concentration in the blood.
Hyperuricemia
MedGen UID:
149260
Concept ID:
C0740394
Disease or Syndrome
An abnormally high level of uric acid in the blood.
Elevated circulating parathyroid hormone level
MedGen UID:
167805
Concept ID:
C0857973
Finding
An abnormal increased concentration of parathyroid hormone.
Distal renal tubular acidosis
MedGen UID:
853429
Concept ID:
C1704380
Disease or Syndrome
A type of renal tubular acidosis characterized by a failure of acid secretion by the alpha intercalated cells of the cortical collecting duct of the distal nephron. The urine cannot be acidified below a pH of 5.3, associated with acidemia and hypokalemia.
Abnormal circulating calcium concentration
MedGen UID:
868059
Concept ID:
C4022450
Finding
Any deviation from the normal concentration of calcium in the blood circulation.
Astigmatism
MedGen UID:
2473
Concept ID:
C0004106
Disease or Syndrome
Astigmatism (from the Greek 'a' meaning absence and 'stigma' meaning point) is a condition in which the parallel rays of light entering the eye through the refractive media are not focused on a single point. Both corneal and noncorneal factors contribute to refractive astigmatism. Corneal astigmatism is mainly the result of an aspheric anterior surface of the cornea, which can be measured readily by means of a keratometer; in a small fraction of cases (approximately 1 in 10) the effect is neutralized by the back surface. The curvature of the back surface of the cornea is not considered in most studies, because it is more difficult to measure; moreover, in the case of severe corneal astigmatism, there is evidence that both surfaces have the same configuration. Noncorneal factors are errors in the curvature of the 2 surfaces of the crystalline lens, irregularity in the refractive index of the lens, and an eccentric lens position. Since the cornea is the dominant component of the eye's refracting system, a highly astigmatic cornea is likely to result in a similarly astigmatic ocular refraction (summary by Clementi et al., 1998).
Hypermetropia
MedGen UID:
43780
Concept ID:
C0020490
Disease or Syndrome
An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry.
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPrimary hypomagnesemia
Follow this link to review classifications for Primary hypomagnesemia in Orphanet.

Professional guidelines

PubMed

Witteveen JE, van Thiel S, Romijn JA, Hamdy NA
Eur J Endocrinol 2013 Mar;168(3):R45-53. Epub 2013 Feb 20 doi: 10.1530/EJE-12-0528. PMID: 23152439
Zhang W, Doherty M, Bardin T, Barskova V, Guerne PA, Jansen TL, Leeb BF, Perez-Ruiz F, Pimentao J, Punzi L, Richette P, Sivera F, Uhlig T, Watt I, Pascual E
Ann Rheum Dis 2011 Apr;70(4):563-70. Epub 2011 Jan 7 doi: 10.1136/ard.2010.139105. PMID: 21216817
Assadi F
Iran J Kidney Dis 2008 Jul;2(3):115-22. PMID: 19377223

Recent clinical studies

Etiology

Glaudemans B, van der Wijst J, Scola RH, Lorenzoni PJ, Heister A, van der Kemp AW, Knoers NV, Hoenderop JG, Bindels RJ
J Clin Invest 2009 Apr;119(4):936-42. Epub 2009 Mar 23 doi: 10.1172/JCI36948. PMID: 19307729Free PMC Article
Groenestege WM, Thébault S, van der Wijst J, van den Berg D, Janssen R, Tejpar S, van den Heuvel LP, van Cutsem E, Hoenderop JG, Knoers NV, Bindels RJ
J Clin Invest 2007 Aug;117(8):2260-7. doi: 10.1172/JCI31680. PMID: 17671655Free PMC Article
Schlingmann KP, Sassen MC, Weber S, Pechmann U, Kusch K, Pelken L, Lotan D, Syrrou M, Prebble JJ, Cole DE, Metzger DL, Rahman S, Tajima T, Shu SG, Waldegger S, Seyberth HW, Konrad M
J Am Soc Nephrol 2005 Oct;16(10):3061-9. Epub 2005 Aug 17 doi: 10.1681/ASN.2004110989. PMID: 16107578
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
Unachak K, Louthrenoo O, Katanyuwong K
J Med Assoc Thai 2002 Nov;85(11):1226-31. PMID: 12546321

Diagnosis

Wang P, Qian Y, Gu C, Zhi X, Pu L, Yan D, Shu J, Lv L, Cai C
Clin Chim Acta 2021 Dec;523:469-475. Epub 2021 Oct 28 doi: 10.1016/j.cca.2021.10.033. PMID: 34755648
Schlingmann KP, Sassen MC, Weber S, Pechmann U, Kusch K, Pelken L, Lotan D, Syrrou M, Prebble JJ, Cole DE, Metzger DL, Rahman S, Tajima T, Shu SG, Waldegger S, Seyberth HW, Konrad M
J Am Soc Nephrol 2005 Oct;16(10):3061-9. Epub 2005 Aug 17 doi: 10.1681/ASN.2004110989. PMID: 16107578
Unachak K, Louthrenoo O, Katanyuwong K
J Med Assoc Thai 2002 Nov;85(11):1226-31. PMID: 12546321
Geven WB, Monnens LA, Willems JL
Miner Electrolyte Metab 1993;19(4-5):308-13. PMID: 8264518
Yamamoto T, Kabata H, Yagi R, Takashima M, Itokawa Y
Magnesium 1985;4(2-3):153-64. PMID: 2995735

Therapy

Nesibe A, Sinasi O
J Pediatr Endocrinol Metab 2012;25(5-6):599-602. PMID: 22876566
Groenestege WM, Thébault S, van der Wijst J, van den Berg D, Janssen R, Tejpar S, van den Heuvel LP, van Cutsem E, Hoenderop JG, Knoers NV, Bindels RJ
J Clin Invest 2007 Aug;117(8):2260-7. doi: 10.1172/JCI31680. PMID: 17671655Free PMC Article
Unachak K, Louthrenoo O, Katanyuwong K
J Med Assoc Thai 2002 Nov;85(11):1226-31. PMID: 12546321
Yamamoto T, Kabata H, Yagi R, Takashima M, Itokawa Y
Magnesium 1985;4(2-3):153-64. PMID: 2995735
Suh SM, Tashjian AH Jr, Matsuo N, Parkinson DK, Fraser D
J Clin Invest 1973 Jan;52(1):153-60. doi: 10.1172/JCI107159. PMID: 4345201Free PMC Article

Prognosis

Rouka E, Liakopoulos V, Gourgoulianis KI, Hatzoglou C, Zarogiannis SG
Medicina (Kaunas) 2019 Jul 26;55(8) doi: 10.3390/medicina55080409. PMID: 31357502Free PMC Article
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
Unachak K, Louthrenoo O, Katanyuwong K
J Med Assoc Thai 2002 Nov;85(11):1226-31. PMID: 12546321
Yamamoto T, Kabata H, Yagi R, Takashima M, Itokawa Y
Magnesium 1985;4(2-3):153-64. PMID: 2995735
Lombeck I, Ritzl F, Schnippering HG, Michael H, Bremer HJ, Feinendegen LE, Kosenow W
Z Kinderheilkd 1975;118(4):249-58. doi: 10.1007/BF00492330. PMID: 1130118

Clinical prediction guides

Rouka E, Liakopoulos V, Gourgoulianis KI, Hatzoglou C, Zarogiannis SG
Medicina (Kaunas) 2019 Jul 26;55(8) doi: 10.3390/medicina55080409. PMID: 31357502Free PMC Article
Konrad M, Schlingmann KP, Gudermann T
Am J Physiol Renal Physiol 2004 Apr;286(4):F599-605. doi: 10.1152/ajprenal.00312.2003. PMID: 15001450
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
Challa A, Papaefstathiou I, Lapatsanis D, Tsolas O
Acta Paediatr 1995 Sep;84(9):1075-8. doi: 10.1111/j.1651-2227.1995.tb13830.x. PMID: 8652964
Suh SM, Tashjian AH Jr, Matsuo N, Parkinson DK, Fraser D
J Clin Invest 1973 Jan;52(1):153-60. doi: 10.1172/JCI107159. PMID: 4345201Free PMC Article

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