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Disease Profile

Renal hypomagnesemia 2

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

All ages

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ICD-10

E83.4

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Magnesium loss, isolated renal; Magnesium wasting, renal; HOMG2;

Categories

Congenital and Genetic Diseases; Kidney and Urinary Diseases; Metabolic disorders

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 34528

Definition
A mild form of familial primary hypomagnesemia (FPH), characterized by extreme weakness, tetany and convulsions. Secondary disturbances in calcium excretion are observed.

Epidemiology
To date, only one large pedigree with 18 affected individuals has been reported in the literature.

Clinical description
Autosomal dominant primary hypomagnesemia with hypocalciuria (ADPHH) can be detected in childhood or in adult life. Most affected individuals are asymptomatic but patients may suffer from generalized convulsions. In adulthood, chondrocalcinosis may be observed.

Etiology
ADPHH is caused by mutations in the FXYD2 gene (11q23; mutation p.Gly41Arg) which encodes the gamma subunit of the Na+/K+-ATPase, localized on the basolateral membranes of nephron epithelial cells and expressed in the distal convoluted tubule. A similar phenotype is observed in about 45-65% of patients with mutations in the HNF1Bgene (hepatocyte nuclear factor 1B; 17q12), which encodes a transcription factor expressed in renal epithelia. Indeed, this transcription factor stimulates transcriptional expression of the FXYD2 gene. Hypokalemia is observed in 46% of patients with HNF1B gene mutations.

Diagnostic methods
Diagnosis relies on a hypomagnesemia, hypermagnesuria and hypocalciuria phenotype. In patients with FXYD2 mutations, no hypokalemia or metabolic alkalosis is observed. In contrast, in patients with HNF1B mutations, hypokalemia can be detected. Diagnosis is confirmed by the genetic screening of the genes FXYD2 and HNF1B.

Differential diagnosis
Differential diagnosis includes all causes of renal hypomagnesemia, particularly diseases associated with hypocalciuria such as Gitelman syndrome, EAST syndrome and familial primary hypomagnesemia with normocalciuria and normocalcemia (see these terms).

Antenatal diagnosis
Prenatal diagnosis relies on detection of bilateral hyperechogenic kidneys of normal or moderately enlarged size by ultrasound in patients with HNF1B mutations.

Genetic counseling
Transmission is autosomal dominant. Genetic counseling may be proposed and the recurrence risk is 50%.

Management and treatment
Management is mainly symptomatic and includes oral magnesium supplements.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
5%-29% of people have these symptoms
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Chondrocalcinosis
Calcium deposits in joints
0000934
Generalized muscle weakness
0003324
Hypocalciuria
Low urine calcium levels
0003127
Hypokalemia
Low blood potassium levels
0002900
Hypomagnesemia
Low blood magnesium levels
0002917
Renal magnesium wasting
0005567
Seizure
0001250

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Renal hypomagnesemia 2. Click on the link to view a sample search on this topic.