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Test ID RBART Bartter Syndrome Gene Panel, Varies


Ordering Guidance


The genes associated with Gitelman syndrome (SLC12A3) and autosomal dominant familial hypocalciuric hypercalcemia (FHH) (CASR) are not included on this panel. If testing for these disorders and Bartter syndrome on a single panel is desired, order RSCGP / Nephrocalcinosis, Nephrolithiasis, and Renal Electrolyte Imbalance Gene Panel, Varies. It is inappropriate to order both this test and RSCGP on the same patient because the genes on this panel are included on the RSCGP panel.

 

Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Mutation, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

 

Customization of this panel and single gene analysis for any gene present on this panel are available. For more information, see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Specimen Required


Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred)/Refrigerated


Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Hereditary Renal Genetic Testing Patient Information (T918)

Useful For

Providing a genetic evaluation for patients with a personal or family history suggestive of Bartter syndrome

 

Establishing a diagnosis of Bartter syndrome

Method Name

Sequence Capture and Amplicon-Based Next-Generation Sequencing (NGS)

Reporting Name

Bartter Syndrome Gene Panel

Specimen Type

Varies

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Clinical Information

Bartter syndrome (BS) is a rare, hereditary tubulopathy of highly variable severity that can cause renal salt-wasting in infants and young children due to impaired sodium/chloride reabsorption in the thick ascending limb of the nephron.(1)

 

Characteristic clinical features are hypokalemic, hypochloremic metabolic alkalosis and normal blood pressure despite hyperreninemia and hyperaldosteronism.(1) Children with BS have hypercalciuria and normal serum magnesium levels and may present with symptoms in early childhood or before birth. These symptoms distinguish BS from a more common and milder renal salt-wasting disorder called Gitelman syndrome, which features hypocalciuria and low serum magnesium levels and typically presents after 6 years of age. Autosomal dominant hypocalcemia may resemble Bartter syndrome in patients with a markedly activating gain-of-function variant but is distinguishable from BS by mode of inheritance and the presence of hypocalcemia and hypomagnesemia.

 

Age of onset and disease severity is highly variable in Bartter syndrome. The most severe form, antenatal Bartter syndrome (also known as hyperprostaglandin E syndrome or neonatal Bartter syndrome), typically results in polyhydramnios, leading to premature birth. Infants often demonstrate failure to thrive and have significant polyuria resulting in risk for life-threatening salt and water loss.

 

There are four subtypes of Bartter syndrome that typically present antenatally. BS type 1, caused by biallelic alterations in SLC12A1, may also feature fever, vomiting, and nephrocalcinosis in infancy. BS type 2, caused by biallelic variants in KCNJ1, causes symptoms like BS type 1, but patients may demonstrate transient hyperkalemia and acidosis. BS type 4a, caused by biallelic alterations in BSND, and BS type 4b, caused by alterations in CLCNKA and CLCNKB, may be accompanied by sensorineural deafness in addition to renal salt-wasting and related symptoms. Type 4b is also inherited in an autosomal recessive (or biallelic) pattern or can result from digenic inheritance.

 

Classic Bartter syndrome, also known as type 3, is the second major form of BS and is caused by alterations in CLCNKB. All BS type 3 patients have marked hypochloremia. Age of onset varies in BS type 3 and may correlate with genotype, with individuals with truncating variants presenting earlier in life. Individuals with BS type 3 may present antenatally with polyhydramnios, during infancy with failure to thrive and lethargy, or in adolescence or adulthood with symptoms of chronic hypokalemia, such as constipation, muscle cramps, salt-craving, nocturia, and vomiting. Nephrocalcinosis is uncommon in BS type 3, and patients are usually normocalciuric but may still have severe electrolyte imbalances.

 

A third from of BS called transient neonatal Bartter syndrome (BS type 5), is associated with severe polyhydramnios and extreme salt wasting at birth that spontaneously resolves in the first few months of life in surviving patients. BS type 5 is caused by variants in MAGED2 inherited in an X-linked recessive pattern.

 

Although there is some phenotypic overlap between Bartter syndrome, Gitelman syndrome, and autosomal dominant hypocalcemia, they have different genetic causes.

 

This panel does not include the genes associated with Gitelman syndrome (SLC12A3) or autosomal dominant hypocalcemia (CASR). If simultaneous genetic testing for Bartter syndrome, Gitelman syndrome and/or autosomal dominant hypocalcemic hypercalciuria is desired, order RSCGP / Nephrocalcinosis, Nephrolithiasis, and Renal Electrolyte Imbalance Gene Panel, Varies.

Reference Values

An interpretive report will be provided.

Interpretation

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(2) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Clinical Reference

1. Fulchiero R, Seo-Mayer P. Bartter Syndrome and Gitelman Syndrome. Pediatr Clin North Am. 2019 Feb;66(1):121-134.

2. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424.

Day(s) Performed

Varies

Report Available

28 to 42 days

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81404

81406

81407

81479

81479 (if appropriate for government payers)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
RBART Bartter Syndrome Gene Panel 51966-0

 

Result ID Test Result Name Result LOINC Value
618101 Test Description 62364-5
618102 Specimen 31208-2
618103 Source 31208-2
618104 Result Summary 50397-9
618105 Result 82939-0
618106 Interpretation 69047-9
618107 Additional Results In Process
618108 Resources 99622-3
618109 Additional Information 48767-8
618110 Method 85069-3
618111 Genes Analyzed 48018-6
618112 Disclaimer 62364-5
618113 Released By 18771-6