Rare Gastroenterology News

Disease Profile

Bartter 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.

Unknown

Age of onset

Antenatal

ICD-10

E26.8

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.

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 wasting; Bartter's syndrome; Hypokalemic alkalosis with hypercalciuria

Categories

Metabolic disorders

Summary

Bartter syndrome is a group of very similar kidney disorders that cause an imbalance of potassium, sodium, chloride, and related molecules in the body.

In some cases, Bartter syndrome becomes apparent before birth. The disorder can cause polyhydramnios, which is an increased volume of fluid surrounding the fetus (amniotic fluid). Polyhydramnios increases the risk of premature birth.

Beginning in infancy, affected individuals often fail to grow and gain weight at the expected rate (failure to thrive). They lose excess amounts of salt (sodium chloride) in their urine, which leads to dehydration, constipation, and increased urine production (polyuria). In addition, large amounts of calcium are lost through the urine (hypercalciuria), which can cause weakening of the bones (osteopenia). Some of the calcium is deposited in the kidneys as they are concentrating urine, leading to hardening of the kidney tissue (nephrocalcinosis). Bartter syndrome is also characterized by low levels of potassium in the blood (hypokalemia), which can result in muscle weakness, cramping, and fatigue. Rarely, affected children develop hearing loss caused by abnormalities in the inner ear (sensorineural deafness).

Two major forms of Bartter syndrome are distinguished by their age of onset and severity. One form begins before birth (antenatal) and is often life-threatening. The other form, often called the classical form, begins in early childhood and tends to be less severe. Once the genetic causes of Bartter syndrome were identified, researchers also split the disorder into different types based on the genes involved. Types I, II, and IV have the features of antenatal Bartter syndrome. Because type IV is also associated with hearing loss, it is sometimes called antenatal Bartter syndrome with sensorineural deafness. Type III usually has the features of classical Bartter syndrome.

This disease summary is from MedlinePlus Genetics, an online health information resource from the National Institutes of Health.

Symptoms

The signs and symptoms associated with Bartter syndrome can vary depending on the form of Bartter syndrome an affected individual has.[1] The antenatal forms (beginning before birth) can be life-threatening, while the classical form, beginning in early childhood, tends to be less severe.[2]

The antenatal forms of Bartter syndrome (types I, II and IV) may first be characterized by abnormally high levels of amniotic fluid surrounding the affected fetus (polyhydramnios); premature delivery; and possibly life-threatening salt (sodium-chloride) loss.[2][3] Affected newborns may experience excessive urination (polyuria) and life-threatening episodes of fever and dehydration. Vomiting and diarrhea may also occur. Some affected infants have distinctive facial features (triangular face, prominent forehead, large eyes, protruding ears, and drooping mouth), failure to thrive, delayed growth, and/or intellectual disability.[1] Individuals with type IV may also have sensorineural deafness (hearing loss caused by abnormalities in the inner ear).[2]

Classical Bartter syndrome typically becomes apparent in childhood and is characterized by muscle weakness, cramping, spasms, and fatigue. Excessive thirst (polydipsia), excessive urination and the need to urinate at night (nocturia) may also be present. This can lead to dehydration. Some children crave salt. Additional symptoms include constipation, vomiting, elevated body temperature, growth delay and developmental delay.[1]

Some individuals with Bartter syndrome have significant electrolyte imbalances which can lead to irregular heartbeats (cardiac arrhythmias). This can increase the risk for sudden cardiac arrest. Another complication is excessive levels of calcium in the kidneys (nephrocalcinosis). This can lead to blood in the urine, vomiting, and fever. Over time, this calcium buildup can affect kidney function.[1]

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
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality

[ more ]

0001939
5%-29% of people have these symptoms
Hyperparathyroidism
Elevated blood parathyroid hormone level
0000843
Hypocalciuria
Low urine calcium levels
0003127
Hypomagnesemia
Low blood magnesium levels
0002917
Percent of people who have these symptoms is not available through HPO
Abnormal choroid morphology
0000610
Abnormal retinal vascular morphology
Abnormality of retina blood vessels
0008046
Abnormal sclera morphology
0000591
Abnormally large globe
Increased size of eyes
Large eyes

[ more ]

0001090
Autosomal recessive inheritance
0000007
Chondrocalcinosis
Calcium deposits in joints
0000934
Congenital onset
Symptoms present at birth
0003577
Constipation
0002019
Decreased glomerular filtration rate
0012213
Dehydration
0001944
Diarrhea
Watery stool
0002014
Edema
Fluid retention
Water retention

[ more ]

0000969
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Fetal polyuria
0001563
Fever
0001945
Frontal bossing
0002007
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Generalized muscle weakness
0003324
Global developmental delay
0001263
Global glomerulosclerosis
0004737
Hydrops fetalis
0001789
Hyperactive renin-angiotensin system
0000841
Hyperaldosteronism
Elevated plasma aldosterone
Increased aldosterone
Increased aldosterone production

[ more ]

0000859
Hypercalcemia
High blood calcium levels
Increased calcium in blood

[ more ]

0003072
Hypercalciuria
Elevated urine calcium levels
0002150
Hyperchloriduria
Increased urinary chloride
0002914
Hypernatriuria
0012605
Hyperprostaglandinuria
High urine prostaglandin levels
0003527
Hypochloremia
Low blood chloride levels
0003113
Hypokalemia
Low blood potassium levels
0002900
Hypokalemic hypochloremic metabolic alkalosis
0004909
Hypokalemic metabolic alkalosis
0001960
Hyponatremia
Low blood sodium levels
0002902
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Hyposthenuria
0003158
Hypotension
Low blood pressure
0002615
Impaired platelet aggregation
0003540
Impaired reabsorption of chloride
0005579
Increased circulating renin level
Elevated blood renin level
0000848
Increased serum prostaglandin E2
0003566
Increased urinary potassium
0003081
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Low-to-normal blood pressure
0002632
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Macrotia
Large ears
0000400
Motor delay
0001270
Muscle spasm
0003394
Muscular hypotonia
Low or weak muscle tone
0001252
Nephrocalcinosis
Too much calcium deposited in kidneys
0000121
Osteopenia
0000938
Paresthesia
Pins and needles feeling
Tingling

[ more ]

0003401
Polydipsia
Extreme thirst
0001959
Polyhydramnios
High levels of amniotic fluid
0001561
Polyuria
Increased urine output
0000103
Premature birth
Premature delivery of affected infants
Preterm delivery

[ more ]

0001622
Prominent for

Cause

Bartter syndrome may be caused by mutations in any one of several genes; the genetic cause in each case corresponds to the type of Bartter syndrome each affected individual has. Type I results from mutations in the SLC12A1 gene. Type II is caused by mutations in the KCNJ1 gene. Type III results from mutations in the CLCNKB gene. Type IV can be caused by mutations in the BSND gene or from a combination of mutations in the CLCNKA and CLCNKB genes.[2] A final variant, type V, has been associated mutations in the CASR gene.[4] In some people with Bartter syndrome, the genetic cause of the disorder remains unknown; there may be other genes that cause the condition that have not yet been identified.[4]

All of these genes are essential for normal kidney function they are involved in the kidneys' abilities to reabsorb salt. Abnormal changes in these genes impair these abilities, allowing for the loss of excess salt through the urine and also affecting the reabsorption of other things including potassium and calcium. The resulting imbalance of these in the body lead to the signs and symptoms of Bartter syndrome.[2]

 

Diagnosis

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.

Bartter syndrome is usually diagnosed after a combination of tests are performed on an individual with the signs and symptoms of the condition. Laboratory tests include blood tests to measure serum electrolyte levels (specifically magnesium, renin, and aldosterone), and urine tests to determine the presence of prostaglandin E2 and urine electrolytes (including elevated levels of sodium and potassium).[1]

Antenatal subtypes can be diagnosed before birth (prenatally) when polyhydramnios is present without associated congenital malformations and when there are elevated levels of chloride and aldosterone in the amniotic fluid. Molecular genetic testing can be used to confirm the diagnosis.[1]

Treatment

Treatment of Bartter syndrome depends on the specific symptoms present in each individual and may require the coordinated efforts of a team of specialists. The primary focus of treatment is on restoring the proper balance of fluids and electrolytes in the body.[1] This may include oral potassium (K) supplements, medication such as indomethacin, and potassium-sparing diuretics. In high-stress situations such as illness or trauma, blood electrolyte levels can change rapidly, which may require immediate intravenous treatment.[4][1] Genetic counseling may benefit affected individuals and their families.[1]

Medscape Reference has an article containing additional, detailed information about the management and treatment of Bartter syndrome. Click here to view this information.

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

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • MedlinePlus Genetics contains information on Bartter syndrome. This website is maintained by the National Library of Medicine.
      • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        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 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. 
          Antenatal Bartter syndrome type I
          Antenatal Bartter syndrome type II
          Bartter syndrome type III
          Bartter syndrome type IV A
          Bartter syndrome type IV B
        • 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 Bartter syndrome. Click on the link to view a sample search on this topic.

          References

          1. Bockenhauer D. Bartter's Syndrome. National Organization for Rare Disorders (NORD). 2016; https://rarediseases.org/rare-diseases/bartters-syndrome/.
          2. Bartter syndrome. Genetics Home Reference. February 2011; https://ghr.nlm.nih.gov/condition/bartter-syndrome.
          3. Proesmans W. Threading through the mizmaze of Bartter syndrome. Pediatric Nephrology. July 2006; 21(7):896-902. https://www.ncbi.nlm.nih.gov/pubmed/16773399.
          4. G. Colussi. Bartter syndrome. Orphanet. September 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=112.
          5. Frassetto LA. Bartter syndrome. MedScape Reference. August 8, 2016; https://emedicine.medscape.com/article/238670-overview.

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