Primary Hypomagnesemia

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

Aliases & Classifications for Primary Hypomagnesemia

MalaCards integrated aliases for Primary Hypomagnesemia:

Name: Primary Hypomagnesemia 12 28 14 69
Familial Primary Hypomagnesemia 49 69
Primary Familial Hypomagnesemia 12
Hypomagnesemia 1, Intestinal 69
Homg 12


External Ids:

Disease Ontology 12 DOID:0060879
ICD10 32 E83.4

Summaries for Primary Hypomagnesemia

NIH Rare Diseases : 49 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 hypomagnesemia 2, renal and hypomagnesemia 1, intestinal, and has symptoms including spasm, seizures and polydipsia. 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:

spasm, seizures, polydipsia, polyuria, abdominal pain

MGI Mouse Phenotypes related to Primary Hypomagnesemia:

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

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
Magnesium Sulfate Approved, Investigational, Vet_approved 7487-88-9 24083
2 Analgesics
3 calcium channel blockers
4 Central Nervous System Depressants
5 Tocolytic Agents
6 Anesthetics
7 Peripheral Nervous System Agents
8 Anti-Arrhythmia Agents
9 Anticonvulsants
10 Calcium, Dietary

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 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 28 CLDN16

Anatomical Context for Primary Hypomagnesemia

MalaCards organs/tissues related to Primary Hypomagnesemia:

Testes, Brain

Publications for Primary Hypomagnesemia

Articles related to Primary Hypomagnesemia:

(show all 16)
# Title Authors Year
Novel TRPM6 mutations in 21 families with primary hypomagnesemia and secondary hypocalcemia. ( 16107578 )
Primary hypomagnesemia in Thai infants: a case report with 7 years follow-up and review of literature. ( 12546321 )
Primary hypomagnesemia with secondary hypocalcemia in an infant. ( 11910142 )
Primary hypomagnesemia caused by isolated magnesium malabsorption: atypical case in adult. ( 10337938 )
Familial primary hypomagnesemia complicated with brain atrophy and cardiomyopathy. ( 9297931 )
Primary hypomagnesemia with a probable double magnesium transport defect. ( 2352584 )
Primary hypomagnesemia with a probable double magnesium transport defect. ( 2710272 )
Effect of serum magnesium concentration on renal handling of phosphate in a patient with primary hypomagnesemia. ( 3396512 )
Primary hypomagnesemia with secondary hypocalcemia. Report of a case and review of the world literature. ( 2995735 )
Parathyroid hormone secretion and responsiveness to parathyroid hormone in primary hypomagnesemia. ( 6853131 )
Primary hypomagnesemia. I. Absorption Studies. ( 1130118 )
Pathogenesis of hypocalcemia in primary hypomagnesemia: normal end-organ responsiveness to parathyroid hormone, impaired parathyroid gland function. ( 4345201 )
Primary hypomagnesemia with secondary hypocalcemia, diarrhea and insensitivity to parathyroid hormone. ( 5032685 )
Distribution of divalent cations at the cellular level during primary hypomagnesemia in infancy. ( 5053136 )
Primary hypomagnesemia with secondary hypocalcemia in an infant. ( 5637791 )
Congenital primary hypomagnesemia, an inborn error of metabolism? ( 5586087 )

Variations for Primary Hypomagnesemia

ClinVar genetic disease variations for Primary Hypomagnesemia:

6 (show all 17)
# Gene Variation Type Significance SNP ID Assembly Location
1 CLDN16 NM_006580.3(CLDN16): c.823A> T (p.Lys275Ter) single nucleotide variant Pathogenic rs387906880 GRCh37 Chromosome 3, 190127730: 190127730
2 CLDN16 NM_006580.3(CLDN16): c.445C> T (p.Arg149Ter) single nucleotide variant Pathogenic rs104893720 GRCh37 Chromosome 3, 190122568: 190122568
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.571G> A (p.Gly191Arg) single nucleotide variant Pathogenic rs104893722 GRCh37 Chromosome 3, 190122694: 190122694
5 CLDN16 NM_006580.3(CLDN16): c.593G> A (p.Gly198Asp) single nucleotide variant Pathogenic rs104893723 GRCh37 Chromosome 3, 190126103: 190126103
6 CLDN16 NM_006580.3(CLDN16): c.212T> G (p.Met71Arg) single nucleotide variant Pathogenic rs104893724 GRCh37 Chromosome 3, 190106120: 190106120
7 CLDN16 NM_006580.3(CLDN16): c.500T> C (p.Leu167Pro) single nucleotide variant Pathogenic rs104893725 GRCh37 Chromosome 3, 190122623: 190122623
8 CLDN16 NM_006580.3(CLDN16): c.695T> G (p.Phe232Cys) single nucleotide variant Pathogenic rs104893726 GRCh37 Chromosome 3, 190126205: 190126205
9 CLDN16 NM_006580.3(CLDN16): c.698G> A (p.Gly233Asp) single nucleotide variant Pathogenic rs104893727 GRCh37 Chromosome 3, 190126208: 190126208
10 CLDN16 NM_006580.3(CLDN16): c.704C> T (p.Ser235Phe) single nucleotide variant Pathogenic rs104893728 GRCh37 Chromosome 3, 190126214: 190126214
11 CLDN16 NM_006580.3(CLDN16): c.453G> T (p.Leu151Phe) single nucleotide variant Pathogenic rs104893729 GRCh37 Chromosome 3, 190122576: 190122576
12 CLDN16 NM_006580.3(CLDN16): c.452T> G (p.Leu151Trp) single nucleotide variant Pathogenic rs104893730 GRCh37 Chromosome 3, 190122575: 190122575
13 CLDN16 NM_006580.3(CLDN16): c.434T> C (p.Leu145Pro) single nucleotide variant Pathogenic rs104893731 GRCh37 Chromosome 3, 190122557: 190122557
14 CLDN16 NM_006580.3(CLDN16): c.350G> A (p.Trp117Ter) single nucleotide variant Pathogenic rs104893732 GRCh37 Chromosome 3, 190120151: 190120151
15 CLDN16 CLDN16, LEU151PRO undetermined variant Pathogenic
16 CLDN16 NM_006580.3(CLDN16): c.831T> G (p.Tyr277Ter) single nucleotide variant Pathogenic rs121908543 GRCh37 Chromosome 3, 190127738: 190127738
17 CLDN16 NM_006580.3(CLDN16): c.678delT (p.Gly227Valfs) deletion Pathogenic GRCh37 Chromosome 3, 190126188: 190126188

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 transport GO:0006810 9.7 ATP6V0A4 CLDN16 FXYD2 KCNA1 SLC2A2 SLC5A1
2 carbohydrate transport GO:0008643 9.46 SLC2A2 SLC5A1
3 excretion GO:0007588 9.43 ATP6V0A4 CLDN16
4 glucose transport GO:0015758 9.4 SLC2A2 SLC5A1
5 glucose transmembrane transport GO:1904659 9.37 SLC2A2 SLC5A1
6 calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules GO:0016338 9.32 CLDN16 CLDN19
7 positive regulation of ossification GO:0045778 9.26 PTH TOB2
8 ion transport GO:0006811 9.1 ATP6V0A4 CLDN16 FXYD2 KCNA1 SLC5A1 TRPM6
9 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

9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
51 Novoseek
54 OMIM via Orphanet
58 PubMed
66 SNOMED-CT via Orphanet
68 Tocris
70 UMLS via Orphanet
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