MCID: PRM237
MIFTS: 43

Primary Hypomagnesemia

Categories: Rare diseases, Genetic diseases, Metabolic diseases, Nephrological diseases

Aliases & Classifications for Primary Hypomagnesemia

MalaCards integrated aliases for Primary Hypomagnesemia:

Name: Primary Hypomagnesemia 12 24 29 14 69
Familial Primary Hypomagnesemia 50 69
Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis 24
Primary Familial Hypomagnesemia 12
Isolated Renal Hypomagnesemia 24
Hypomagnesemia 1, Intestinal 69
Homg 12

Classifications:



External Ids:

Disease Ontology 12 DOID:0060879
ICD10 33 E83.4

Summaries for Primary Hypomagnesemia

NIH Rare Diseases : 50 the following summary is from orphanet, a european reference portal for information on rare diseases and orphan drugs.orpha number: 34526disease definitionfamilial primary hypomagnesemia (fph) is a rare mineral absorption and transport disorder characterized by a selective defect in renal or intestinal magnesium (mg) absorption, resulting in a low mg concentration in the blood.epidemiologyto date, more than 500 cases have been described in the literature.clinical descriptionclinical manifestations include weakness, fatigue, increased neuromuscular excitability (muscle fasciculation, cramps, tremor carpopedal spasms, numbness in the hands and tetany), central nervous system manifestations (lethargy, drowsiness, depression, agitation and generalized seizures), and cardiac manifestations (atrial or ventricular tachycardia, and premature contractions). chronic hypomagnesemia may be associated with chondrocalcinosis. hypomagnesemia is frequently accompanied by hypocalcemia and sometimes by hypokalemia. depending on the renal segment involved, fph can be associated with hypercalcuria (when the defect of magnesium reabsorption is in the thick ascending limb of henle's loop) or with hypocalcuria or normocalcuria (when the defect of magnesium reabsorption is in distal convoluted tubule). the severity of the clinical manifestations and the age of onset is variable (depends on the implicated transporter and type of inheritance. severe and early presentation is observed in primary hypomagnesemia with secondary hypocalcemia (phsh, recessive inheritance; see this term), while the mild phenotype is observed in older children and adults in dominant diseases. other hereditary renal diseases are frequently associated with hypomagnesemia such as salt losing tubulopathies: classic bartter syndrome, gitelman syndrome, east syndrome, renal cysts and diabetes syndrome and autosomal dominant hypocalcemia (see these terms).etiologyrenal reabsorption of mg occurs in the loop of henle via a passive paracellular transport process implicating claudin-16 and claudin-19 while in the intestine and in the distal convoluted tubule (dct), reabsorption is achieved by an active process mediated by trpm6. fph is caused by mutations in genes encoding key proteins with direct or indirect involvement in active mg handling, such as cldn16, cldn19, cnnm2, egf, fxyd2, kcna1, hnf1b and trpm6.diagnostic methodsclinically, chvostek's (twitching of facial muscles in response to tapping over the area of the facial nerve) and trousseau's (carpopedal spasm resulting from ischemia) signs can detect hypomagnesemia in a specific and sensitive manner. diagnosis is also established by simultaneous evaluation of serum mg and urinary mg excretion. presence of hypomagnesemia with adapted urinary mg excretion ( 2 mmol/24h or fe >2%) indicates a renal origin. in mixed intestinal and renal hypomagnesemia (phsh), the renal reabsorption defect is only observed after an intravenous magnesium load test. diagnosis is confirmed by molecular screening of genes involved in fph.differential diagnosisdifferential diagnosis includes isolated mg malabsorption, hypoparathyroidism and drug toxicity (diuretics, aminoglycosides, proton pump inhibitors, pentamidin, egf receptor antagonists, calcineurin inhibitors and platin salts).genetic counselingtransmission is autosomal recessive or autosomal dominant.management and treatmenttreatment of fph involves substitution with oral mg. in cases of intolerance, patients may be treated with intramuscular mg sulfate. treatment and doses should be adjusted according to gastrointestinal tolerance and clinical manifestations. intravenous mg and calcium therapies may be given during symptomatic attacks.prognosisprognosis is highly dependent on the rapidity of diagnosis and treatment. complications or death resulting from untreated convulsions or tetany may be observed in certain forms of fph.visit the orphanet disease page for more resources. last updated: 2/24/2014

MalaCards based summary : Primary Hypomagnesemia, also known as familial primary hypomagnesemia, is related to familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis and familial primary hypomagnesemia with normocalciuria and normocalcemia, and has symptoms including abdominal pain, polyuria and seizures. An important gene associated with Primary Hypomagnesemia is CLDN16 (Claudin 16), and among its related pathways/superpathways are Mineral absorption and Carbohydrate digestion and absorption. The drugs Magnesium citrate and Magnesium oxide have been mentioned in the context of this disorder. Affiliated tissues include testes, kidney and bone, and related phenotype is homeostasis/metabolism.

Disease Ontology : 12 A metal metabolism disorder characterized by very low serum magnesium levels often with secondary hypocalcemia with onset typically in the first months of life.

Related Diseases for Primary Hypomagnesemia

Graphical network of the top 20 diseases related to Primary Hypomagnesemia:



Diseases related to Primary Hypomagnesemia

Symptoms & Phenotypes for Primary Hypomagnesemia

UMLS symptoms related to Primary Hypomagnesemia:


abdominal pain, polyuria, seizures, polydipsia, spasm

MGI Mouse Phenotypes related to Primary Hypomagnesemia:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.32 ADCY10 ATP6V0A4 CLDN16 CLDN19 KCNA1 MGAM

Drugs & Therapeutics for Primary Hypomagnesemia

Drugs for Primary Hypomagnesemia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 76)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Magnesium citrate Approved Phase 4
2
Magnesium oxide Approved Phase 4 1309-48-4 14792
3
Magnesium Sulfate Approved, Vet_approved Phase 4 7487-88-9 24083
4
Cholecalciferol Approved, Nutraceutical Phase 4 67-97-0 6221 10883523 5280795
5
Ergocalciferol Approved, Nutraceutical Phase 4 50-14-6 5280793
6
Vitamin D Approved, Nutraceutical, Vet_approved Phase 4 1406-16-2
7
Levulinic acid Experimental Phase 4 123-76-2 11579
8 Pharmaceutical Solutions Phase 4
9 Antacids Phase 4,Phase 1,Phase 2
10 Anticoagulants Phase 4
11 Anti-Ulcer Agents Phase 4,Phase 1,Phase 2
12 Calcium, Dietary Phase 4
13 Cathartics Phase 4
14 Chelating Agents Phase 4
15 Gastrointestinal Agents Phase 4,Phase 1,Phase 2
16 Laxatives Phase 4
17 Bone Density Conservation Agents Phase 4
18 Ergocalciferols Phase 4
19 Micronutrients Phase 4
20 Trace Elements Phase 4
21 Vitamins Phase 4
22 Citrate Nutraceutical Phase 4
23
Citric Acid Nutraceutical, Vet_approved Phase 4 77-92-9 311
24 Calciferol Nutraceutical Phase 4
25 Vitamin D2 Nutraceutical Phase 4
26
Amphotericin B Approved, Investigational Phase 2 1397-89-3 14956 5280965
27
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
28
Amiloride Approved Phase 1, Phase 2 2016-88-8, 2609-46-3 16231
29
Eplerenone Approved Phase 1, Phase 2 107724-20-9 150310 443872
30
Indomethacin Approved, Investigational Phase 1, Phase 2 53-86-1 3715
31
Omeprazole Approved, Investigational, Vet_approved Phase 1, Phase 2 73590-58-6 4594
32
Magnesium Hydroxide Approved Phase 1, Phase 2 1309-42-8
33 Anti-Bacterial Agents Phase 2
34 Antifungal Agents Phase 2
35 Anti-Infective Agents Phase 2
36 Antiparasitic Agents Phase 2
37 Antiprotozoal Agents Phase 2
38 Cytochrome P-450 CYP2C9 Inhibitors Phase 2
39 Cytochrome P-450 CYP3A Inhibitors Phase 2
40 Cytochrome P-450 Enzyme Inhibitors Phase 2
41 Hormone Antagonists Phase 2,Phase 1
42 Hormones Phase 2,Phase 1
43 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2,Phase 1
44 Liposomal amphotericin B Phase 2
45 Steroid Synthesis Inhibitors Phase 2
46 Analgesics Phase 1, Phase 2
47 Analgesics, Non-Narcotic Phase 1, Phase 2
48 Anti-Inflammatory Agents Phase 1, Phase 2
49 Anti-Inflammatory Agents, Non-Steroidal Phase 1, Phase 2
50 Antirheumatic Agents Phase 1, Phase 2

Interventional clinical trials:

(show all 17)

id Name Status NCT ID Phase Drugs
1 Magnesium and Metabolic Syndrome Completed NCT00603499 Phase 4
2 The Absorption of Magnesium Oxide Compared to Citrate in Healthy Subjects Completed NCT00994006 Phase 4
3 Electrolyte Profile, Nutritional Status and Ileostomy Formation. Recruiting NCT02036346 Phase 4
4 Vitamin D Deficiency and Postoperative Hypocalcemia Active, not recruiting NCT01632514 Phase 4 Cholecalciferol
5 Magnesium Deficiency In Patients Hospitalized in Internal Medicine Wards Not yet recruiting NCT03088852 Phase 4 Magnesium Citrate 100 MG
6 PROPHESSOR: AmBisome in Antifungal Primary Prophylaxis Treatment of High Risk Patients Undergoing Allogeneic Stem Cell Transplantation Completed NCT00326157 Phase 2 AmBisome
7 Input of the Use of Indometacin in Gitelman Syndrome as Compared to Potassium Sparing Diuretics Completed NCT01146197 Phase 1, Phase 2 TREATMENT
8 Magnesium Supplementation for Hypomagnesemia in Chronic Kidney Disease Completed NCT02216877 Phase 1, Phase 2 Mablet 360 mg;Placebo
9 Magnesium Treatment of Inflammation in Disorders of Glucose Homeostasis Completed NCT01980459 Phase 1
10 Magnesium Replacement Therapy to Prevent Acute Renal Failure in Critically Ill Patients Completed NCT01700998 Magnesium;Placebo
11 Prevalence and Intervention of Hypomagnesemia in Users of Proton-pump Inhibitors Completed NCT02518659
12 Acid Suppressive Therapy - Review of Appropriateness Completed NCT02259270
13 Pilot Study: Hypovitaminosis D, Hyperparathyroidism and Hypomagnesemia in Patients With Congestive Heart Failure Completed NCT00887666
14 Prophylaxis of Magnesium-rich Mineral Water to Prevent Hypomagnesemia Induced by an Anti-EGFR (OPTIMAG) Recruiting NCT03146338
15 Feasibility of Using an Integrated Consent Model to Compare Two Standard of Care Regimens for the Management of Hypomagnesemia From Anti-Cancer Therapies Recruiting NCT02690012
16 Effects of Proton Pump Inhibitors on Kidney Transplant Recipients Active, not recruiting NCT03123796
17 Effect of Magnesium Sulfate Infusion Rate on Magnesium Retention in Critically Ill Patients Terminated NCT01426165 Magnesium Sulfate

Search NIH Clinical Center for Primary Hypomagnesemia

Genetic Tests for Primary Hypomagnesemia

Genetic tests related to Primary Hypomagnesemia:

id Genetic test Affiliating Genes
1 Primary Hypomagnesemia 29 24 CLDN16

Anatomical Context for Primary Hypomagnesemia

MalaCards organs/tissues related to Primary Hypomagnesemia:

39
Testes, Kidney, Bone, Heart, Brain

Publications for Primary Hypomagnesemia

Articles related to Primary Hypomagnesemia:

(show all 16)
id Title Authors Year
1
Novel TRPM6 mutations in 21 families with primary hypomagnesemia and secondary hypocalcemia. ( 16107578 )
2005
2
Primary hypomagnesemia in Thai infants: a case report with 7 years follow-up and review of literature. ( 12546321 )
2002
3
Primary hypomagnesemia with secondary hypocalcemia in an infant. ( 11910142 )
2002
4
Primary hypomagnesemia caused by isolated magnesium malabsorption: atypical case in adult. ( 10337938 )
1999
5
Familial primary hypomagnesemia complicated with brain atrophy and cardiomyopathy. ( 9297931 )
1997
6
Primary hypomagnesemia with a probable double magnesium transport defect. ( 2352584 )
1990
7
Primary hypomagnesemia with a probable double magnesium transport defect. ( 2710272 )
1989
8
Effect of serum magnesium concentration on renal handling of phosphate in a patient with primary hypomagnesemia. ( 3396512 )
1988
9
Primary hypomagnesemia with secondary hypocalcemia. Report of a case and review of the world literature. ( 2995735 )
1985
10
Parathyroid hormone secretion and responsiveness to parathyroid hormone in primary hypomagnesemia. ( 6853131 )
1983
11
Primary hypomagnesemia. I. Absorption Studies. ( 1130118 )
1975
12
Pathogenesis of hypocalcemia in primary hypomagnesemia: normal end-organ responsiveness to parathyroid hormone, impaired parathyroid gland function. ( 4345201 )
1973
13
Primary hypomagnesemia with secondary hypocalcemia, diarrhea and insensitivity to parathyroid hormone. ( 5032685 )
1972
14
Distribution of divalent cations at the cellular level during primary hypomagnesemia in infancy. ( 5053136 )
1972
15
Primary hypomagnesemia with secondary hypocalcemia in an infant. ( 5637791 )
1968
16
Congenital primary hypomagnesemia, an inborn error of metabolism? ( 5586087 )
1967

Variations for Primary Hypomagnesemia

ClinVar genetic disease variations for Primary Hypomagnesemia:

6 (show all 16)
id Gene Variation Type Significance SNP ID Assembly Location
1 CLDN16 NM_006580.3(CLDN16): c.445C> T (p.Arg149Ter) single nucleotide variant Pathogenic rs104893720 GRCh37 Chromosome 3, 190122568: 190122568
2 CLDN16 NM_006580.3(CLDN16): c.715G> A (p.Gly239Arg) single nucleotide variant Pathogenic rs104893721 GRCh37 Chromosome 3, 190126225: 190126225
3 CLDN16 NM_006580.3(CLDN16): c.571G> A (p.Gly191Arg) single nucleotide variant Pathogenic rs104893722 GRCh37 Chromosome 3, 190122694: 190122694
4 CLDN16 NM_006580.3(CLDN16): c.593G> A (p.Gly198Asp) single nucleotide variant Pathogenic rs104893723 GRCh37 Chromosome 3, 190126103: 190126103
5 CLDN16 NM_006580.3(CLDN16): c.212T> G (p.Met71Arg) single nucleotide variant Pathogenic rs104893724 GRCh37 Chromosome 3, 190106120: 190106120
6 CLDN16 NM_006580.3(CLDN16): c.500T> C (p.Leu167Pro) single nucleotide variant Pathogenic rs104893725 GRCh37 Chromosome 3, 190122623: 190122623
7 CLDN16 NM_006580.3(CLDN16): c.695T> G (p.Phe232Cys) single nucleotide variant Pathogenic rs104893726 GRCh37 Chromosome 3, 190126205: 190126205
8 CLDN16 NM_006580.3(CLDN16): c.698G> A (p.Gly233Asp) single nucleotide variant Pathogenic rs104893727 GRCh37 Chromosome 3, 190126208: 190126208
9 CLDN16 NM_006580.3(CLDN16): c.704C> T (p.Ser235Phe) single nucleotide variant Pathogenic rs104893728 GRCh37 Chromosome 3, 190126214: 190126214
10 CLDN16 NM_006580.3(CLDN16): c.453G> T (p.Leu151Phe) single nucleotide variant Pathogenic rs104893729 GRCh37 Chromosome 3, 190122576: 190122576
11 CLDN16 NM_006580.3(CLDN16): c.452T> G (p.Leu151Trp) single nucleotide variant Pathogenic rs104893730 GRCh37 Chromosome 3, 190122575: 190122575
12 CLDN16 NM_006580.3(CLDN16): c.434T> C (p.Leu145Pro) single nucleotide variant Pathogenic rs104893731 GRCh37 Chromosome 3, 190122557: 190122557
13 CLDN16 NM_006580.3(CLDN16): c.350G> A (p.Trp117Ter) single nucleotide variant Pathogenic rs104893732 GRCh37 Chromosome 3, 190120151: 190120151
14 CLDN16 CLDN16, LEU151PRO undetermined variant Pathogenic
15 CLDN16 NM_006580.3(CLDN16): c.831T> G (p.Tyr277Ter) single nucleotide variant Pathogenic rs121908543 GRCh37 Chromosome 3, 190127738: 190127738
16 CLDN16 NM_006580.3(CLDN16): c.823A> T (p.Lys275Ter) single nucleotide variant Pathogenic rs387906880 GRCh37 Chromosome 3, 190127730: 190127730

Expression for Primary Hypomagnesemia

Search GEO for disease gene expression data for Primary Hypomagnesemia.

Pathways for Primary Hypomagnesemia

Pathways related to Primary Hypomagnesemia according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 10.84 FXYD2 SLC5A1 TRPM6
2 10.57 FXYD2 MGAM SLC2A2 SLC5A1

GO Terms for Primary Hypomagnesemia

Cellular components related to Primary Hypomagnesemia according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 9.96 ADCY10 ATP6V0A4 CLDN16 CLDN19 FXYD2 KCNA1
2 integral component of membrane GO:0016021 9.9 ADCY10 ATP6V0A4 CLDN16 CLDN19 FXYD2 KCNA1
3 brush border membrane GO:0031526 9.13 ATP6V0A4 SLC5A1 TRPM6
4 apical plasma membrane GO:0016324 9.1 ATP6V0A4 KCNA1 MGAM SLC2A2 SLC5A1 TRPM6

Biological processes related to Primary Hypomagnesemia according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.76 KCNA1 SLC2A2 SLC5A1 TRPM6
2 transport GO:0006810 9.7 ATP6V0A4 CLDN16 FXYD2 KCNA1 SLC2A2 SLC5A1
3 carbohydrate transport GO:0008643 9.43 SLC2A2 SLC5A1
4 excretion GO:0007588 9.4 ATP6V0A4 CLDN16
5 glucose transport GO:0015758 9.37 SLC2A2 SLC5A1
6 glucose transmembrane transport GO:1904659 9.32 SLC2A2 SLC5A1
7 calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules GO:0016338 9.26 CLDN16 CLDN19
8 ion transport GO:0006811 9.1 ATP6V0A4 CLDN16 FXYD2 KCNA1 SLC5A1 TRPM6
9 positive regulation of ossification GO:0045778 8.96 PTH TOB2

Molecular functions related to Primary Hypomagnesemia according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 ion channel activity GO:0005216 8.8 FXYD2 KCNA1 TRPM6

Sources for Primary Hypomagnesemia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....