BARTS3
MCID: BRT042
MIFTS: 44

Bartter Syndrome, Type 3 (BARTS3)

Categories: Blood diseases, Ear diseases, Endocrine diseases, Genetic diseases, Metabolic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Bartter Syndrome, Type 3

MalaCards integrated aliases for Bartter Syndrome, Type 3:

Name: Bartter Syndrome, Type 3 58 13 41 74
Bartter Syndrome Type 3 12 54 60 30 6
Classic Bartter Syndrome 12 60 76
Barts3 58 12 76
Bartter Syndrome, Classic 58 56
Bartter Disease Type 3 12 15
Bartter Syndrome Type Iii 60
Bartter Syndrome Classic 54
Adult Bartter Syndrome 60
Bartter Syndrome 3 76

Characteristics:

Orphanet epidemiological data:

60
classic bartter syndrome
Inheritance: Autosomal recessive; Age of onset: Adolescent,Adult,Childhood,Infancy;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
variable age of onset
clinical variation


HPO:

33
bartter syndrome, type 3:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare renal diseases


External Ids:

Disease Ontology 12 DOID:0110144
OMIM 58 607364
MeSH 45 D001477
ICD10 34 E26.8
ICD10 via Orphanet 35 E26.8
UMLS via Orphanet 75 C1846343
Orphanet 60 ORPHA93605
UMLS 74 C1846343

Summaries for Bartter Syndrome, Type 3

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 93605Disease definitionClassic Bartter syndrome is a type of Bartter syndrome (see this term), characterized by a milder clinical picture than the antenatal/infantile subtype, and presenting with failure to thrive, hypokalemic alkalosis, increased levels of plasma renin and aldosterone, low blood pressure and vascular resistance to angiotensin II.EpidemiologyExact prevalence of Classic Bartter syndrome is not known. It is by far the most frequent type of Bartter syndrome.Clinical descriptionClassic Bartter syndrome is characterized by a milder clinical picture with a wide phenotypic heterogeneity when compared to other subtypes of Bartter syndrome. Only one third of the patients present with maternal polyhydramnios which usually does not lead to prematurity. Patients usually present after neonatal period with failure to thrive, fatigue, muscle weakness, cramps and carpopedal spasms. Hypokalemia and alkalosis are common. Polyuria and hypostenuria/isosthenuria are variable, as is hypercalciuria. Few patients develop medullary nephrocalcinosis.EtiologyMutation in CLCNKB gene (1p36), encoding a basolateral chloride channel ClCKb, has been identified as the most frequent cause of classic Bartter syndrome. Both the chloride channels, ClCKa and ClCKb are expressed in thick ascending limb of the loop of Henle (TALH), ClCKa is exclusively expressed in the ascending limb, while ClCKb is also expressed in distal convoluted tubule (DCT), thereby explaining the pronounced DCT features (similar to Gitelman syndrome; see this term) in some patients with CLCNKB mutations. CLCNKB mutations define classic Bartter syndrome; however, genes other than CLCNKB (those that are usually associated with other types of Bartter syndrome) may less commonly cause the classic, less severe phenotype, such as SLC12A1 and KCNJ1. Rarely, patients with BSND mutation may show a mild phenotype of salt loss associated with deafness.Diagnostic methodsDiagnosis is based on the clinical picture, plasma and urine electrolytes (sodium, potassium, chloride, bicarbonate, magnesium, calcium), renin and aldosterone levels. Calcium levels in the urine may be normal or slightly increased. Genetic testing provides the definite diagnosis.Differential diagnosisThe differential diagnosis includes pseudo-Bartter syndrome (diuretic abuse, surreptitious vomiting), cystic fibrosis, Gitelman syndrome, and celiac disease (see these terms).Antenatal diagnosisDiagnostic testing of amniocytes might be indicated for mothers of affected children, or potential heterozygouscarriers (close relatives of affected individuals).Genetic counselingInheritance is autosomal recessive.Management and treatmentTreatment includes oral potassium supplements, non-steroidal anti-inflammatory drugs (e.g. indometacin) and possibly potassium-sparing diuretics. In stressful situations (additional diseases, surgical procedures, trauma) blood electrolyte levels may change rapidly, requiring prompt and vigorous treatment.PrognosisLife expectancy may be reduced in severe cases but renal failure is rare. Quality of life may be poor, growth rate reduced, and medicalization/hospitalization rate high.Visit the Orphanet disease page for more resources.

MalaCards based summary : Bartter Syndrome, Type 3, also known as bartter syndrome type 3, is related to bartter syndrome, type 4b, neonatal, with sensorineural deafness and gitelman syndrome, and has symptoms including generalized muscle weakness and polyuria. An important gene associated with Bartter Syndrome, Type 3 is CLCNKB (Chloride Voltage-Gated Channel Kb), and among its related pathways/superpathways is Diuretics Pathway, Pharmacodynamics. Affiliated tissues include kidney, testes and retina, and related phenotypes are hypocalciuria and hypotension

Disease Ontology : 12 A Bartter disease that has material basis in homozygous or compound heterozygous mutation in the kidney chloride channel B gene (CLCNKB) on chromosome 1p36.

OMIM : 58 Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997). Patients with antenatal (or neonatal) forms of Bartter syndrome (e.g., BARTS1, 601678) typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012). (607364)

UniProtKB/Swiss-Prot : 76 Bartter syndrome 3: A form of Bartter syndrome, an autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria.

Related Diseases for Bartter Syndrome, Type 3

Diseases in the Bartter Disease family:

Bartter Syndrome, Type 3 Bartter Syndrome Type 4

Diseases related to Bartter Syndrome, Type 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 25)
# Related Disease Score Top Affiliating Genes
1 bartter syndrome, type 4b, neonatal, with sensorineural deafness 32.2 CLCNKA CLCNKB
2 gitelman syndrome 31.4 BSND CLCNKB KCNJ1 REN SLC12A1 SLC12A3
3 nephrocalcinosis 30.1 CLCNKB KCNJ1 SLC12A1 SLC12A3
4 nephrolithiasis 30.0 BSND CLCNKB KCNJ1 SLC12A1
5 bartter disease 29.9 BSND CLCNKA CLCNKB KCNJ1 REN SLC12A1
6 primary hypomagnesemia 11.2
7 bartter syndrome, type 2, antenatal 11.1
8 bartter syndrome, type 1, antenatal 11.1
9 bartter syndrome, type 4a, neonatal, with sensorineural deafness 11.1
10 deafness, autosomal recessive 96 10.2 CLCNKA CLCNKB
11 autosomal recessive nonsyndromic deafness 36 10.2 CLCNKA CLCNKB
12 arthrogryposis, distal, type 3 10.2 REN SLC12A3
13 dent disease 1 10.2 CLCNKA CLCNKB
14 polyhydramnios 10.2 CLCNKB KCNJ1 SLC12A1
15 renal hypertension 10.1 REN SLC12A3
16 infantile bartter syndrome with sensorineural deafness 10.1 BSND CLCNKA CLCNKB
17 pseudohypoaldosteronism 10.1 KCNJ1 REN SLC12A3
18 diabetes insipidus 10.1 CLCNKA REN SLC12A1
19 pseudohyperkalemia, familial, 2, due to red cell leak 10.1 KCNJ1 REN
20 mineral metabolism disease 10.0 CLCNKB KCNJ1 REN SLC12A3
21 seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance 10.0 KCNJ1 SLC12A3
22 antenatal bartter syndrome 10.0 BSND KCNJ1 REN SLC12A1
23 growth hormone deficiency 10.0
24 hypokalemia 9.7 BSND CLCNKB KCNJ1 REN SLC12A1 SLC12A3
25 renal tubular transport disease 9.5 BSND CLCNKA CLCNKB KCNJ1 REN SLC12A1

Graphical network of the top 20 diseases related to Bartter Syndrome, Type 3:



Diseases related to Bartter Syndrome, Type 3

Symptoms & Phenotypes for Bartter Syndrome, Type 3

Human phenotypes related to Bartter Syndrome, Type 3:

33 (show all 18)
# Description HPO Frequency HPO Source Accession
1 hypocalciuria 33 occasional (7.5%) HP:0003127
2 hypotension 33 HP:0002615
3 dehydration 33 HP:0001944
4 hypokalemia 33 HP:0002900
5 generalized muscle weakness 33 HP:0003324
6 hyperaldosteronism 33 HP:0000859
7 renal salt wasting 33 HP:0000127
8 increased circulating renin level 33 HP:0000848
9 renal potassium wasting 33 HP:0000128
10 increased urinary potassium 33 HP:0003081
11 hypokalemic metabolic alkalosis 33 HP:0001960
12 polyuria 33 HP:0000103
13 hyperactive renin-angiotensin system 33 HP:0000841
14 impaired reabsorption of chloride 33 HP:0005579
15 abnormal choroid morphology 33 HP:0000610
16 hyperchloriduria 33 HP:0002914
17 abnormal retinal vascular morphology 33 HP:0008046
18 abnormal sclera morphology 33 HP:0000591

Symptoms via clinical synopsis from OMIM:

58
Metabolic Features:
dehydration
hypokalemic metabolic alkalosis

Muscle Soft Tissue:
generalized muscle weakness

Endocrine Features:
hyperactive renin-angiotensin system
increased plasma renin
increased plasma aldosterone

Cardiovascular Vascular:
low blood pressure

Laboratory Abnormalities:
hypokalemia
increased urinary potassium
increased serum bicarbonate
increased urinary chloride
hypocalciuria or normocalciuria

Genitourinary Kidneys:
renal salt wasting
renal potassium wasting
polyuria
impaired reabsorption of chloride
nephrocalcinosis is absent

Head And Neck Eyes:
multifocal yellow-white geographic, solid, choroidal lesions along the retinal vascular arcades
b-scan ultrasound shows echogenic, placoid calcified lesions at the level of the sclera and choroid
optical coherence tomography shows normal retina and retinal pigment epithelium overlying the sclerochoroidal lesions

Clinical features from OMIM:

607364

UMLS symptoms related to Bartter Syndrome, Type 3:


generalized muscle weakness, polyuria

MGI Mouse Phenotypes related to Bartter Syndrome, Type 3:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.02 BSND CBSL CLCNKA KCNJ1 PTGES REN
2 hematopoietic system MP:0005397 9.91 BSND CBSL IMPDH1 KCNJ1 PTGES REN
3 homeostasis/metabolism MP:0005376 9.85 BSND CBSL CLCNKA CLCNKB KCNJ1 PTGES
4 mortality/aging MP:0010768 9.65 BSND CBSL CLCNKA DDX41 KCNJ1 PDXK
5 renal/urinary system MP:0005367 9.28 BSND CBSL CLCNKA CLCNKB KCNJ1 REN

Drugs & Therapeutics for Bartter Syndrome, Type 3

Search Clinical Trials , NIH Clinical Center for Bartter Syndrome, Type 3

Genetic Tests for Bartter Syndrome, Type 3

Genetic tests related to Bartter Syndrome, Type 3:

# Genetic test Affiliating Genes
1 Bartter Syndrome Type 3 30 CLCNKB

Anatomical Context for Bartter Syndrome, Type 3

MalaCards organs/tissues related to Bartter Syndrome, Type 3:

42
Kidney, Testes, Retina

Publications for Bartter Syndrome, Type 3

Articles related to Bartter Syndrome, Type 3:

# Title Authors Year
1
Bartter Syndrome Type 3: Phenotype-Genotype Correlation and Favorable Response to Ibuprofen. ( 29900164 )
2018
2
Clinical and Genetic Spectrum of Bartter Syndrome Type 3. ( 28381550 )
2017
3
Paving the way for Bartter syndrome type 3 drug discovery: a hope from basic research. ( 28598505 )
2017
4
ClC-K chloride channels: emerging pathophysiology of Bartter syndrome type 3. ( 25810436 )
2015
5
Bartter syndrome type 3 in an elderly complicated with adrenocorticotropin-deficiency. ( 24965226 )
2014
6
Bartter syndrome type 3: an unusual cause of nephrolithiasis. ( 11865110 )
2002
7
Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome. ( 10906158 )
2000
8
Mutations in the chloride channel gene, CLCNKB, leading to a mixed Bartter-Gitelman phenotype. ( 11102542 )
2000
9
Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. ( 9326936 )
1997

Variations for Bartter Syndrome, Type 3

UniProtKB/Swiss-Prot genetic disease variations for Bartter Syndrome, Type 3:

76
# Symbol AA change Variation ID SNP ID
1 CLCNKB p.Pro124Leu VAR_001624 rs121909131
2 CLCNKB p.Ala204Thr VAR_001625 rs121909132
3 CLCNKB p.Ala349Asp VAR_001626 rs121909134
4 CLCNKB p.Tyr432His VAR_001627 rs121909135
5 CLCNKB p.Arg438Cys VAR_001628 rs121909133

ClinVar genetic disease variations for Bartter Syndrome, Type 3:

6 (show all 21)
# Gene Variation Type Significance SNP ID Assembly Location
1 CLCNKB NM_000085.4(CLCNKB): c.371C> T (p.Pro124Leu) single nucleotide variant Pathogenic rs121909131 GRCh37 Chromosome 1, 16374412: 16374412
2 CLCNKB NM_000085.4(CLCNKB): c.371C> T (p.Pro124Leu) single nucleotide variant Pathogenic rs121909131 GRCh38 Chromosome 1, 16047917: 16047917
3 CLCNKB NM_000085.4(CLCNKB): c.610G> A (p.Ala204Thr) single nucleotide variant Pathogenic rs121909132 GRCh37 Chromosome 1, 16375032: 16375032
4 CLCNKB NM_000085.4(CLCNKB): c.610G> A (p.Ala204Thr) single nucleotide variant Pathogenic rs121909132 GRCh38 Chromosome 1, 16048537: 16048537
5 CLCNKB NM_000085.4(CLCNKB): c.1312C> T (p.Arg438Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs121909133 GRCh37 Chromosome 1, 16378219: 16378219
6 CLCNKB NM_000085.4(CLCNKB): c.1312C> T (p.Arg438Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs121909133 GRCh38 Chromosome 1, 16051724: 16051724
7 CLCNKB NM_000085.4(CLCNKB): c.1046C> A (p.Ala349Asp) single nucleotide variant Pathogenic rs121909134 GRCh37 Chromosome 1, 16377088: 16377088
8 CLCNKB NM_000085.4(CLCNKB): c.1046C> A (p.Ala349Asp) single nucleotide variant Pathogenic rs121909134 GRCh38 Chromosome 1, 16050593: 16050593
9 CLCNKB NM_000085.4(CLCNKB): c.1294T> C (p.Tyr432His) single nucleotide variant Pathogenic rs121909135 GRCh37 Chromosome 1, 16378039: 16378039
10 CLCNKB NM_000085.4(CLCNKB): c.1294T> C (p.Tyr432His) single nucleotide variant Pathogenic rs121909135 GRCh38 Chromosome 1, 16051544: 16051544
11 CLCNKB CLCNKB, DEL deletion Pathogenic
12 CLCNKB CLCNKB, IVS7AS, A-G, -2 single nucleotide variant Pathogenic
13 CLCNKB CLCNKB, DEL deletion Pathogenic
14 CLCNKB NM_000085.4(CLCNKB): c.1897del (p.Leu633Terfs) deletion Likely pathogenic rs863224858 GRCh37 Chromosome 1, 16382221: 16382221
15 CLCNKB NM_000085.4(CLCNKB): c.1897del (p.Leu633Terfs) deletion Likely pathogenic rs863224858 GRCh38 Chromosome 1, 16055726: 16055726
16 CLCNKB NM_000085.4(CLCNKB): c.1381dupA (p.Ile461Asnfs) duplication Pathogenic rs1057516207 GRCh38 Chromosome 1, 16051793: 16051793
17 CLCNKB NM_000085.4(CLCNKB): c.1381dupA (p.Ile461Asnfs) duplication Pathogenic rs1057516207 GRCh37 Chromosome 1, 16378288: 16378288
18 CLCNKB NM_000085.4(CLCNKB): c.18dup (p.Leu7Alafs) duplication Pathogenic GRCh38 Chromosome 1, 16044510: 16044510
19 CLCNKB NM_000085.4(CLCNKB): c.18dup (p.Leu7Alafs) duplication Pathogenic GRCh37 Chromosome 1, 16371005: 16371005
20 CLCNKA NM_004070.3(CLCNKA): c.55C> T (p.Gln19Ter) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 16022674: 16022674
21 CLCNKA NM_004070.3(CLCNKA): c.55C> T (p.Gln19Ter) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 16349169: 16349169

Expression for Bartter Syndrome, Type 3

Search GEO for disease gene expression data for Bartter Syndrome, Type 3.

Pathways for Bartter Syndrome, Type 3

Pathways related to Bartter Syndrome, Type 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.56 BSND CLCNKA CLCNKB KCNJ1 SLC12A1 SLC12A3

GO Terms for Bartter Syndrome, Type 3

Cellular components related to Bartter Syndrome, Type 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 secretory granule lumen GO:0034774 8.8 IMPDH1 IMPDH2 PDXK

Biological processes related to Bartter Syndrome, Type 3 according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.88 CLCNKA CLCNKB KCNJ1 SLC12A1 SLC12A3
2 transmembrane transport GO:0055085 9.87 CLCNKA CLCNKB SLC12A1 SLC12A3
3 regulation of ion transmembrane transport GO:0034765 9.72 CLCNKA CLCNKB KCNJ1
4 chloride transport GO:0006821 9.58 BSND CLCNKA CLCNKB
5 positive regulation of type I interferon production GO:0032481 9.56 DDX41 TBK1
6 cell volume homeostasis GO:0006884 9.54 SLC12A1 SLC12A3
7 purine nucleotide biosynthetic process GO:0006164 9.52 IMPDH1 IMPDH2
8 potassium ion homeostasis GO:0055075 9.51 SLC12A1 SLC12A3
9 potassium ion import across plasma membrane GO:1990573 9.5 KCNJ1 SLC12A1 SLC12A3
10 purine ribonucleoside monophosphate biosynthetic process GO:0009168 9.49 IMPDH1 IMPDH2
11 GTP biosynthetic process GO:0006183 9.46 IMPDH1 IMPDH2
12 chloride ion homeostasis GO:0055064 9.43 SLC12A1 SLC12A3
13 lymphocyte proliferation GO:0046651 9.37 IMPDH1 IMPDH2
14 ion transmembrane transport GO:0034220 9.35 BSND CLCNKA CLCNKB KCNJ1 SLC12A1
15 excretion GO:0007588 9.33 CLCNKA CLCNKB KCNJ1
16 GMP biosynthetic process GO:0006177 9.26 IMPDH1 IMPDH2
17 chloride transmembrane transport GO:1902476 9.02 BSND CLCNKA CLCNKB SLC12A1 SLC12A3

Molecular functions related to Bartter Syndrome, Type 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chloride channel activity GO:0005254 9.54 BSND CLCNKA CLCNKB
2 potassium:chloride symporter activity GO:0015379 9.43 SLC12A1 SLC12A3
3 cation:chloride symporter activity GO:0015377 9.4 SLC12A1 SLC12A3
4 sodium ion transmembrane transporter activity GO:0015081 9.32 SLC12A1 SLC12A3
5 IMP dehydrogenase activity GO:0003938 9.26 IMPDH1 IMPDH2
6 sodium:chloride symporter activity GO:0015378 9.16 SLC12A1 SLC12A3
7 sodium:potassium:chloride symporter activity GO:0008511 8.96 SLC12A1 SLC12A3
8 voltage-gated chloride channel activity GO:0005247 8.62 CLCNKA CLCNKB

Sources for Bartter Syndrome, Type 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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