Rare Gastroenterology News

Disease Profile

Gitelman syndrome

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.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Childhood

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ICD-10

N15.8

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.

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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)

Potassium and magnesium depletion; Hypomagnesemia-hypokalemia, primary renotubular, with hypocalciuria; Familial hypokalemia-hypomagnesemia;

Categories

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

Summary

Gitelman syndrome is a kidney function disorder that causes an imbalance of charged atoms (ions) in the body, including ions of potassium, magnesium, and calcium.[1] It is usually diagnosed during late childhood or adulthood.[2] More common symptoms include fatigue, salt craving, thirst, frequent urination, muscle cramping, muscle weakness, dizziness, tingling or numbness, low blood pressure, and heart palpitations.[3] Gitelman syndrome can be caused by changes (mutations) in the SLC12A3 or CLCNKB genes and is inherited in an autosomal recessive manner.[1][4] Treatment may include supplementation of potassium and magnesium, and a high sodium and high potassium diet.[2]

Symptoms

Signs and symptoms of Gitelman syndrome tend to present in adolescents and adults, but occasionally present in infants and young children. Signs and symptoms in children and adults vary, but may include:

A preference for salty foods (salt craving)
Muscle weakness
Fatigue
Limited sports performance or endurance
Episodes of fainting
Cramps
Muscle spasms
Numbness or tingling (such as of the face)
Growth delay
Delayed puberty
Short stature
Excessive thirst
Abdominal pain

Adults with Gitelman syndrome may also experience dizziness, vertigo, excessive amount of urine, urinating more at night, heart palpitations, joint pain, and vision problems.[3]

Other possible symptoms include low blood pressure, a painful joint condition called, chondrocalcinosis, prolonged QT interval (a rare heart problem that may cause irregular heartbeat, fainting, or sudden death), episodes of elevated body temperature, vomiting, constipation, bed wetting, and paralysis.[3] Additional rare symptoms have been described in single cases.[3]

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
80%-99% of people have these symptoms
Hypokalemia
Low blood potassium levels
0002900
30%-79% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain

[ more ]

0002027
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Hypomagnesemia
Low blood magnesium levels
0002917
Low-to-normal blood pressure
0002632
Muscle weakness
Muscular weakness
0001324
Prolonged QT interval
0001657
5%-29% of people have these symptoms
Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay

[ more ]

0000823
Enuresis
0000805
Hypermagnesemia
High blood magnesium levels
0002918
Hypocalcemia
Low blood calcium levels
0002901
Insulin resistance
Body fails to respond to insulin
0000855
Metabolic alkalosis
0200114
Muscle spasm
0003394
Nausea and vomiting
0002017
Nocturia
0000017
Proteinuria
High urine protein levels
Protein in urine

[ more ]

0000093
Renal potassium wasting
0000128
Salt craving
0030083
1%-4% of people have these symptoms
Abnormal T-wave
0005135
Arthralgia
Joint pain
0002829
Blurred vision
0000622
Cerebral calcification
Abnormal deposits of calcium in the brain
0002514
Chondrocalcinosis
Calcium deposits in joints
0000934
Constipation
0002019
Decreased urinary potassium
0012364
Diabetic ketoacidosis
0001953
Diarrhea
Watery stool
0002014
Excessive daytime somnolence
Excessive daytime sleepiness
More than typical sleepiness during day

[ more ]

0001262
Focal segmental glomerulosclerosis
0000097
Focal-onset seizure
Seizure affecting one half of brain
0007359
Gout
0001997
Graves disease
0100647
Hashimoto thyroiditis
0000872
Headache
Headaches
0002315
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased

[ more ]

0000975
Insomnia
Difficulty staying or falling asleep
0100785
Iron deficiency anemia
0001891
Maternal diabetes
gestational diabetes
0009800
Mitochondrial encephalopathy
0006789
Myalgia
Muscle ache
Muscle pain

[ more ]

0003326
Neoplasm of the pancreas
Cancer of the pancreas
Pancreatic tumor

[ more ]

0002894
Palpitations
Missed heart beat
Skipped heart beat

[ more ]

0001962
Paralysis
Inability to move
0003470
Parathyroid adenoma
0002897
Paresthesia
Pins and needles feeling
Tingling

[ more ]

0003401
Pericardial effusion
Fluid around heart
0001698
Polydipsia
Extreme thirst
0001959
Primary hyperaldosteronism
0011736
Prolonged PR interval
0012248
Prominent U wave
0025072
Raynaud phenomenon
0030880
Renal Fanconi syndrome
0001994
Respiratory distress
Breathing difficulties
Difficulty breathing

[ more ]

0002098
Rhabdomyolysis
Breakdown of skeletal muscle
0003201
Scleroderma
0100324
Seizure
0001250
ST segment depression
0012250
Syncope
Fainting spell
0001279
Tinnitus
Ringing in ears
Ringing in the ears

[ more ]

0000360
Tubulointerstitial nephritis
0001970
Type I diabetes mellitus
Type 1 diabetes
Type I diabetes

[ more ]

0100651

Diagnosis

A diagnosis of Gitelman syndrome may be suspected in children and adults with characteristic symptoms. A number of blood and urine tests aid in the diagnosis of Gitelman syndrome, such as:[3][4]  

Potassium urine test
Blood gases
Blood tests to measure magnesium, aldosterone, and renin
Urine analysis for sodium, potassium, and calcium

Common blood and urine abnormalities found in Gitelman syndrome, include:[4]  

Low levels of potassium in the blood (hypokalemia)
Metabolic alkalosis (too much base in the body)
Low magnesium in the blood (hypomagnesemia)
Low levels of calcium in the urine (hypocalciuria)

Anorexia, bulimia, chronic diarrhea, vomiting, and long term use of laxatives or diuretics can cause similar signs and symptoms. Before a diagnosis of Gitelman syndrome is made these conditions must be ruled out.[5] A careful review of the patient and family health histories, as well as renal ultrasound findings can be helpful in ruling out other causes. 

Genetic testing can confirm a diagnosis of Gitelman syndrome. Tools for finding genetic testing for Gitelman syndrome are available below.

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.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    The mainstay treatment of Gitelman syndrome involves careful monitoring, high-sodium and potassium diet, and oral potassium and magnesium supplements. Intravenous magnesium and/or potassium may be needed if symptoms are severe. People who have low potassium levels despite supplementation and diet, may benefit from potassium-sparing diuretics, renin angiotensin system blockers, pain medications, and/or nonsteroidal anti-inflammatory drugs (NSAIDs).[3][4] 

    The Blanchard A et al., 2017 consensus guideline offers detailed treatment information, including information on drug selection, dosing recommendations, and a listing of drugs that can cause adverse effects in people with Gitelman syndrome. 

    Lastly, people with Gitelman syndrome should have a thorough heart work-up. People with Gitelman syndrome and a prolonged QT interval should avoid drugs that prolong the QT interval. The SADS Foundation offers a tool for learning more about what drugs to avoid.[4]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        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.

        Where to Start

          In-Depth Information

          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Merck Manual for health care professionals provides information on Gitelman syndrome.
          • 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 Gitelman syndrome. Click on the link to view a sample search on this topic.

            Selected Full-Text Journal Articles

            • The Orphanet Journal of Rare Diseases has published an article with information on this condition. This journal is affiliated with the Orphanet reference portal for information on rare diseases and orphan drugs.

              References

              1. Gitelman syndrome. Genetics Home Reference. February 2011; https://ghr.nlm.nih.gov/condition/gitelman-syndrome.
              2. Nine VAM Knoers and Elena N Levtchenko. Gitelman syndrome. Orphanet Journal of Rare Diseases. 2008; 3:22:https://www.ojrd.com/content/3/1/22.
              3. Blanchard A, Bockenhauer D, Bolignano D, Calò LA, Cosyns E, Devuyst O, Ellison DH, Karet Frankl FE, Knoers NV, Konrad M, Lin SH, Vargas-Poussou R. Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2017 Jan; 91(1):24-33. https://www.kidney-international.theisn.org/article/S0085-2538(16)30602-0/fulltext. Accessed 2/22/2018.
              4. Klemmer PJ. Gitelman Syndrome. National Organization for Rare Disorders (NORD). 2015; https://rarediseases.org/rare-diseases/gitelman-syndrome/.
              5. Emmett M, Ellison D. Bartter and Gitelman syndromes. In: Sterns RH, Forman JP. UpToDate. Waltham, MA: UpToDate; Last updated February 7, 2018; Accessed 2/22/2018.
              6. Graziani G, Fedeli C, Moroni L, Cosmai L, Badalamenti S, Ponticelli C. Gitelman syndrome: pathophysiological and clinical aspects. QJM. October, 2010; 103(10):741-748. https://www.ncbi.nlm.nih.gov/pubmed/20650971.
              7. V.V.A.M. Knoers, Elena Levtchenko. Gitelman syndrome. Orphanet. July, 2008; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=358.
              8. Lee JH, Lee J, Han JS. Gitelman's syndrome with vomiting manifested by severe metabolic alkalosis and progressive renal insufficiency. Tohoku J Exp Med. 2013; 231(3):165-169. https://www.ncbi.nlm.nih.gov/pubmed/24162365.

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