MCID: PRM237
MIFTS: 39

Primary Hypomagnesemia

Categories: Rare diseases, Metabolic diseases, Gastrointestinal diseases, Genetic diseases

Aliases & Classifications for Primary Hypomagnesemia

MalaCards integrated aliases for Primary Hypomagnesemia:

Name: Primary Hypomagnesemia 12 29 6 15 73
Familial Primary Hypomagnesemia 53 73
Primary Familial Hypomagnesemia 12
Hypomagnesemia 1, Intestinal 73
Homg 12

Classifications:



External Ids:

Disease Ontology 12 DOID:0060879
ICD10 33 E83.4

Summaries for Primary Hypomagnesemia

NIH Rare Diseases : 53 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.

MalaCards based summary : Primary Hypomagnesemia, also known as familial primary hypomagnesemia, is related to hypomagnesemia 2, renal and hypomagnesemia 1, intestinal, 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 Sulfate and Analgesics have been mentioned in the context of this disorder. Affiliated tissues include testes and brain, 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:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.36 ADCY10 ATP6V0A4 CLDN16 CLDN19 IL36RN KCNA1

Drugs & Therapeutics for Primary Hypomagnesemia

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

(show all 10)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Magnesium Sulfate Approved, Investigational, Vet_approved Not Applicable 7487-88-9 24083
2 Analgesics Not Applicable
3 Anesthetics Not Applicable
4 Anti-Arrhythmia Agents Not Applicable
5 Anticonvulsants Not Applicable
6 calcium channel blockers Not Applicable
7 Calcium, Dietary Not Applicable
8 Central Nervous System Depressants Not Applicable
9 Peripheral Nervous System Agents Not Applicable
10 Tocolytic Agents Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Effect of Magnesium Sulfate Infusion Rate on Magnesium Retention in Critically Ill Patients Terminated NCT01426165 Not Applicable Magnesium Sulfate

Search NIH Clinical Center for Primary Hypomagnesemia

Genetic Tests for Primary Hypomagnesemia

Genetic tests related to Primary Hypomagnesemia:

# Genetic test Affiliating Genes
1 Primary Hypomagnesemia 29 CLDN16

Anatomical Context for Primary Hypomagnesemia

MalaCards organs/tissues related to Primary Hypomagnesemia:

41
Testes, Brain

Publications for Primary Hypomagnesemia

Articles related to Primary Hypomagnesemia:

(show all 17)
# Title Authors Year
1
Novel TRPM6 mutations in 21 families with primary hypomagnesemia and secondary hypocalcemia. ( 16107578 )
2005
2
Primary hypomagnesemia with secondary hypocalcemia in an infant. ( 11910142 )
2002
3
Primary hypomagnesemia in Thai infants: a case report with 7 years follow-up and review of literature. ( 12546321 )
2002
4
[Magnesium metabolism in chronic primary hypomagnesemia] ( 14647662 )
2000
5
Primary hypomagnesemia caused by isolated magnesium malabsorption: atypical case in adult. ( 10337938 )
1999
6
Familial primary hypomagnesemia complicated with brain atrophy and cardiomyopathy. ( 9297931 )
1997
7
Primary hypomagnesemia with a probable double magnesium transport defect. ( 2352584 )
1990
8
Primary hypomagnesemia with a probable double magnesium transport defect. ( 2710272 )
1989
9
Effect of serum magnesium concentration on renal handling of phosphate in a patient with primary hypomagnesemia. ( 3396512 )
1988
10
Primary hypomagnesemia with secondary hypocalcemia. Report of a case and review of the world literature. ( 2995735 )
1985
11
Parathyroid hormone secretion and responsiveness to parathyroid hormone in primary hypomagnesemia. ( 6853131 )
1983
12
Primary hypomagnesemia. I. Absorption Studies. ( 1130118 )
1975
13
Pathogenesis of hypocalcemia in primary hypomagnesemia: normal end-organ responsiveness to parathyroid hormone, impaired parathyroid gland function. ( 4345201 )
1973
14
Distribution of divalent cations at the cellular level during primary hypomagnesemia in infancy. ( 5053136 )
1972
15
Primary hypomagnesemia with secondary hypocalcemia, diarrhea and insensitivity to parathyroid hormone. ( 5032685 )
1972
16
Primary hypomagnesemia with secondary hypocalcemia in an infant. ( 5637791 )
1968
17
Congenital primary hypomagnesemia, an inborn error of metabolism? ( 5586087 )
1967

Variations for Primary Hypomagnesemia

ClinVar genetic disease variations for Primary Hypomagnesemia:

6
(show top 50) (show all 113)
# 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.445C> T (p.Arg149Ter) single nucleotide variant Pathogenic rs104893720 GRCh38 Chromosome 3, 190404779: 190404779
3 CLDN16 NM_006580.3(CLDN16): c.715G> A (p.Gly239Arg) single nucleotide variant Pathogenic rs104893721 GRCh37 Chromosome 3, 190126225: 190126225
4 CLDN16 NM_006580.3(CLDN16): c.715G> A (p.Gly239Arg) single nucleotide variant Pathogenic rs104893721 GRCh38 Chromosome 3, 190408436: 190408436
5 CLDN16 NM_006580.3(CLDN16): c.571G> A (p.Gly191Arg) single nucleotide variant Pathogenic rs104893722 GRCh37 Chromosome 3, 190122694: 190122694
6 CLDN16 NM_006580.3(CLDN16): c.571G> A (p.Gly191Arg) single nucleotide variant Pathogenic rs104893722 GRCh38 Chromosome 3, 190404905: 190404905
7 CLDN16 NM_006580.3(CLDN16): c.593G> A (p.Gly198Asp) single nucleotide variant Pathogenic rs104893723 GRCh37 Chromosome 3, 190126103: 190126103
8 CLDN16 NM_006580.3(CLDN16): c.593G> A (p.Gly198Asp) single nucleotide variant Pathogenic rs104893723 GRCh38 Chromosome 3, 190408314: 190408314
9 CLDN16 NM_006580.3(CLDN16): c.212T> G (p.Met71Arg) single nucleotide variant Pathogenic rs104893724 GRCh37 Chromosome 3, 190106120: 190106120
10 CLDN16 NM_006580.3(CLDN16): c.212T> G (p.Met71Arg) single nucleotide variant Pathogenic rs104893724 GRCh38 Chromosome 3, 190388331: 190388331
11 CLDN16 NM_006580.3(CLDN16): c.500T> C (p.Leu167Pro) single nucleotide variant Pathogenic rs104893725 GRCh37 Chromosome 3, 190122623: 190122623
12 CLDN16 NM_006580.3(CLDN16): c.500T> C (p.Leu167Pro) single nucleotide variant Pathogenic rs104893725 GRCh38 Chromosome 3, 190404834: 190404834
13 CLDN16 NM_006580.3(CLDN16): c.695T> G (p.Phe232Cys) single nucleotide variant Pathogenic rs104893726 GRCh37 Chromosome 3, 190126205: 190126205
14 CLDN16 NM_006580.3(CLDN16): c.695T> G (p.Phe232Cys) single nucleotide variant Pathogenic rs104893726 GRCh38 Chromosome 3, 190408416: 190408416
15 CLDN16 NM_006580.3(CLDN16): c.698G> A (p.Gly233Asp) single nucleotide variant Pathogenic rs104893727 GRCh37 Chromosome 3, 190126208: 190126208
16 CLDN16 NM_006580.3(CLDN16): c.698G> A (p.Gly233Asp) single nucleotide variant Pathogenic rs104893727 GRCh38 Chromosome 3, 190408419: 190408419
17 CLDN16 NM_006580.3(CLDN16): c.704C> T (p.Ser235Phe) single nucleotide variant Pathogenic rs104893728 GRCh37 Chromosome 3, 190126214: 190126214
18 CLDN16 NM_006580.3(CLDN16): c.704C> T (p.Ser235Phe) single nucleotide variant Pathogenic rs104893728 GRCh38 Chromosome 3, 190408425: 190408425
19 CLDN16 NM_006580.3(CLDN16): c.453G> T (p.Leu151Phe) single nucleotide variant Pathogenic rs104893729 GRCh37 Chromosome 3, 190122576: 190122576
20 CLDN16 NM_006580.3(CLDN16): c.453G> T (p.Leu151Phe) single nucleotide variant Pathogenic rs104893729 GRCh38 Chromosome 3, 190404787: 190404787
21 CLDN16 NM_006580.3(CLDN16): c.452T> G (p.Leu151Trp) single nucleotide variant Pathogenic rs104893730 GRCh37 Chromosome 3, 190122575: 190122575
22 CLDN16 NM_006580.3(CLDN16): c.452T> G (p.Leu151Trp) single nucleotide variant Pathogenic rs104893730 GRCh38 Chromosome 3, 190404786: 190404786
23 CLDN16 NM_006580.3(CLDN16): c.434T> C (p.Leu145Pro) single nucleotide variant Pathogenic rs104893731 GRCh37 Chromosome 3, 190122557: 190122557
24 CLDN16 NM_006580.3(CLDN16): c.434T> C (p.Leu145Pro) single nucleotide variant Pathogenic rs104893731 GRCh38 Chromosome 3, 190404768: 190404768
25 CLDN16 NM_006580.3(CLDN16): c.350G> A (p.Trp117Ter) single nucleotide variant Pathogenic rs104893732 GRCh37 Chromosome 3, 190120151: 190120151
26 CLDN16 NM_006580.3(CLDN16): c.350G> A (p.Trp117Ter) single nucleotide variant Pathogenic rs104893732 GRCh38 Chromosome 3, 190402362: 190402362
27 CLDN16 CLDN16, LEU151PRO undetermined variant Pathogenic
28 CLDN16 NM_006580.3(CLDN16): c.831T> G (p.Tyr277Ter) single nucleotide variant Pathogenic rs121908543 GRCh37 Chromosome 3, 190127738: 190127738
29 CLDN16 NM_006580.3(CLDN16): c.831T> G (p.Tyr277Ter) single nucleotide variant Pathogenic rs121908543 GRCh38 Chromosome 3, 190409949: 190409949
30 CLDN16 NM_006580.3(CLDN16): c.823A> T (p.Lys275Ter) single nucleotide variant Pathogenic rs387906880 GRCh37 Chromosome 3, 190127730: 190127730
31 CLDN16 NM_006580.3(CLDN16): c.823A> T (p.Lys275Ter) single nucleotide variant Pathogenic rs387906880 GRCh38 Chromosome 3, 190409941: 190409941
32 CLDN16 NM_006580.3(CLDN16): c.324+10T> C single nucleotide variant Benign rs1491994 GRCh37 Chromosome 3, 190106242: 190106242
33 CLDN16 NM_006580.3(CLDN16): c.324+10T> C single nucleotide variant Benign rs1491994 GRCh38 Chromosome 3, 190388453: 190388453
34 CLDN16 NM_006580.3(CLDN16): c.166delG (p.Ala56Leufs) deletion Benign/Likely benign rs368234054 GRCh37 Chromosome 3, 190106074: 190106074
35 CLDN16 NM_006580.3(CLDN16): c.166delG (p.Ala56Leufs) deletion Benign/Likely benign rs368234054 GRCh38 Chromosome 3, 190388285: 190388285
36 CLDN16 NM_006580.3(CLDN16): c.-82A> G single nucleotide variant Uncertain significance rs886058243 GRCh38 Chromosome 3, 190388038: 190388038
37 CLDN16 NM_006580.3(CLDN16): c.-82A> G single nucleotide variant Uncertain significance rs886058243 GRCh37 Chromosome 3, 190105827: 190105827
38 CLDN16 NM_006580.3(CLDN16): c.-6C> T single nucleotide variant Uncertain significance rs557493885 GRCh38 Chromosome 3, 190388114: 190388114
39 CLDN16 NM_006580.3(CLDN16): c.-6C> T single nucleotide variant Uncertain significance rs557493885 GRCh37 Chromosome 3, 190105903: 190105903
40 CLDN16 NM_006580.3(CLDN16): c.255C> G (p.Phe85Leu) single nucleotide variant Likely benign rs149116671 GRCh38 Chromosome 3, 190388374: 190388374
41 CLDN16 NM_006580.3(CLDN16): c.255C> G (p.Phe85Leu) single nucleotide variant Likely benign rs149116671 GRCh37 Chromosome 3, 190106163: 190106163
42 CLDN16 NM_006580.3(CLDN16): c.*761A> G single nucleotide variant Uncertain significance rs886058248 GRCh38 Chromosome 3, 190410797: 190410797
43 CLDN16 NM_006580.3(CLDN16): c.*761A> G single nucleotide variant Uncertain significance rs886058248 GRCh37 Chromosome 3, 190128586: 190128586
44 CLDN16 NM_006580.3(CLDN16): c.*1178C> T single nucleotide variant Uncertain significance rs533709248 GRCh38 Chromosome 3, 190411214: 190411214
45 CLDN16 NM_006580.3(CLDN16): c.*1178C> T single nucleotide variant Uncertain significance rs533709248 GRCh37 Chromosome 3, 190129003: 190129003
46 CLDN16 NM_006580.3(CLDN16): c.-136T> C single nucleotide variant Uncertain significance rs534883127 GRCh38 Chromosome 3, 190387984: 190387984
47 CLDN16 NM_006580.3(CLDN16): c.-136T> C single nucleotide variant Uncertain significance rs534883127 GRCh37 Chromosome 3, 190105773: 190105773
48 CLDN16 NM_006580.3(CLDN16): c.-5G> A single nucleotide variant Uncertain significance rs777259905 GRCh38 Chromosome 3, 190388115: 190388115
49 CLDN16 NM_006580.3(CLDN16): c.-5G> A single nucleotide variant Uncertain significance rs777259905 GRCh37 Chromosome 3, 190105904: 190105904
50 CLDN16 NM_006580.3(CLDN16): c.880G> A (p.Glu294Lys) single nucleotide variant Uncertain significance rs756192568 GRCh38 Chromosome 3, 190409998: 190409998

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:

# 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:

# Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 9.85 ADCY10 ATP6V0A4 CLDN16 CLDN19 FXYD2 KCNA1
2 integral component of membrane GO:0016021 9.7 ADCY10 ATP6V0A4 CLDN16 CLDN19 FXYD2 KCNA1
3 apical plasma membrane GO:0016324 9.02 ATP6V0A4 KCNA1 MGAM SLC2A2 TRPM6

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

# Name GO ID Score Top Affiliating Genes
1 carbohydrate transport GO:0008643 9.4 SLC2A2 SLC5A1
2 excretion GO:0007588 9.37 ATP6V0A4 CLDN16
3 calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules GO:0016338 9.32 CLDN16 CLDN19
4 glucose transmembrane transport GO:1904659 9.26 SLC2A2 SLC5A1
5 positive regulation of ossification GO:0045778 9.16 PTH TOB2
6 ion transport GO:0006811 9.1 ATP6V0A4 CLDN16 FXYD2 KCNA1 SLC5A1 TRPM6
7 intestinal hexose absorption GO:0106001 8.96 SLC2A2 SLC5A1

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

# 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
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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