MCID: BRT042
MIFTS: 41

Bartter Syndrome, Type 3

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

Aliases & Classifications for Bartter Syndrome, Type 3

MalaCards integrated aliases for Bartter Syndrome, Type 3:

Name: Bartter Syndrome, Type 3 57 13 40 73
Bartter Syndrome Type 3 12 53 59 29 6
Classic Bartter Syndrome 12 59 75
Barts3 57 12 75
Bartter Syndrome, Classic 57 55
Bartter Disease Type 3 12 15
Bartter Syndrome Type Iii 59
Bartter Syndrome Classic 53
Adult Bartter Syndrome 59
Bartter Syndrome 3 75

Characteristics:

Orphanet epidemiological data:

59
classic bartter syndrome
Inheritance: Autosomal recessive; Age of onset: Adolescent,Adult,Childhood,Infancy;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable age of onset
clinical variation


HPO:

32
bartter syndrome, type 3:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare renal diseases


External Ids:

OMIM 57 607364
Disease Ontology 12 DOID:0110144
ICD10 33 E26.8
Orphanet 59 ORPHA93605
UMLS via Orphanet 74 C1846343
ICD10 via Orphanet 34 E26.8
MeSH 44 D001477
UMLS 73 C1846343

Summaries for Bartter Syndrome, Type 3

NIH Rare Diseases : 53 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 1, antenatal and gitelman syndrome, and has symptoms including polyuria and generalized muscle weakness. 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 testes, kidney and retina, and related phenotypes are polyuria and renal salt wasting

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 : 57 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 : 75 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 24)
# Related Disease Score Top Affiliating Genes
1 bartter syndrome, type 1, antenatal 31.7 ATP6V0A4 SLC12A1
2 gitelman syndrome 30.5 BSND CLCNKB KCNJ1 REN SLC12A1 SLC12A3
3 nephrocalcinosis 30.2 CLCNKB KCNJ1 SLC12A1
4 bartter syndrome, type 2, antenatal 10.9
5 bartter syndrome, type 4a, neonatal, with sensorineural deafness 10.9
6 infantile bartter syndrome with sensorineural deafness 10.6 BSND CLCNKB
7 arthrogryposis, distal, type 3 10.5 REN SLC12A3
8 dent disease 1 10.5 CLCNKB KCNJ1
9 renal hypertension 10.4 REN SLC12A3
10 polyhydramnios 10.3 CLCNKB KCNJ1 SLC12A1
11 pseudohypoaldosteronism 10.2 KCNJ1 REN SLC12A3
12 conn's syndrome 10.2 CLCNKB REN SLC12A3
13 impaired renal function disease 10.2 ATP6V0A4 SLC12A1
14 pseudohyperkalemia, familial, 2, due to red cell leak 10.1 KCNJ1 REN
15 apparent mineralocorticoid excess 10.0 ATP6V0A4 CLCNKB REN
16 antenatal bartter syndrome 9.9 BSND KCNJ1 REN SLC12A1
17 cystic kidney disease 9.9
18 nephrolithiasis 9.8
19 nominal aphasia 9.7 CBS TBK1
20 mineral metabolism disease 9.4 ATP6V0A4 CLCNKB KCNJ1 REN SLC12A3
21 bartter disease 9.4 BSND CLCNKB KCNJ1 REN SLC12A1 SLC12A3
22 hypokalemia 9.3 BSND CLCNKB KCNJ1 REN SLC12A1 SLC12A3
23 frontotemporal dementia and/or amyotrophic lateral sclerosis 1 9.3 CBS TBK1
24 renal tubular transport disease 8.7 ATP6V0A4 BSND 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

Symptoms via clinical synopsis from OMIM:

57
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
polyuria
renal potassium wasting
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

Human phenotypes related to Bartter Syndrome, Type 3:

32 (show all 18)
# Description HPO Frequency HPO Source Accession
1 polyuria 32 HP:0000103
2 renal salt wasting 32 HP:0000127
3 renal potassium wasting 32 HP:0000128
4 abnormal sclera morphology 32 HP:0000591
5 abnormal choroid morphology 32 HP:0000610
6 hyperactive renin-angiotensin system 32 HP:0000841
7 increased circulating renin level 32 HP:0000848
8 hyperaldosteronism 32 HP:0000859
9 dehydration 32 HP:0001944
10 hypokalemic metabolic alkalosis 32 HP:0001960
11 hypotension 32 HP:0002615
12 hypokalemia 32 HP:0002900
13 hyperchloriduria 32 HP:0002914
14 increased urinary potassium 32 HP:0003081
15 hypocalciuria 32 occasional (7.5%) HP:0003127
16 generalized muscle weakness 32 HP:0003324
17 impaired reabsorption of chloride 32 HP:0005579
18 abnormality of the retinal vasculature 32 HP:0008046

UMLS symptoms related to Bartter Syndrome, Type 3:


polyuria, generalized muscle weakness

MGI Mouse Phenotypes related to Bartter Syndrome, Type 3:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.7 BSND KCNJ1 PTGES REN SLC12A1 SLC12A3
2 homeostasis/metabolism MP:0005376 9.61 TBK1 ATP6V0A4 BSND CLCNKB KCNJ1 PTGES
3 renal/urinary system MP:0005367 9.23 ATP6V0A4 BSND CLCNKB KCNJ1 REN SLC12A1

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 29 CLCNKB

Anatomical Context for Bartter Syndrome, Type 3

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

41
Testes, Kidney, Retina

Publications for Bartter Syndrome, Type 3

Articles related to Bartter Syndrome, Type 3:

# Title Authors Year
1
Bartter syndrome type 3: an unusual cause of nephrolithiasis. ( 11865110 )
2002

Variations for Bartter Syndrome, Type 3

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

75
# 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 15)
# 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.1046C> A (p.Ala349Asp) single nucleotide variant Pathogenic rs121909134 GRCh37 Chromosome 1, 16377088: 16377088
6 CLCNKB NM_000085.4(CLCNKB): c.1046C> A (p.Ala349Asp) single nucleotide variant Pathogenic rs121909134 GRCh38 Chromosome 1, 16050593: 16050593
7 CLCNKB NM_000085.4(CLCNKB): c.1294T> C (p.Tyr432His) single nucleotide variant Pathogenic rs121909135 GRCh37 Chromosome 1, 16378039: 16378039
8 CLCNKB NM_000085.4(CLCNKB): c.1294T> C (p.Tyr432His) single nucleotide variant Pathogenic rs121909135 GRCh38 Chromosome 1, 16051544: 16051544
9 CLCNKB CLCNKB, DEL deletion Pathogenic
10 CLCNKB CLCNKB, IVS7AS, A-G, -2 single nucleotide variant Pathogenic
11 CLCNKB CLCNKB, DEL deletion Pathogenic
12 CLCNKB NM_000085.4(CLCNKB): c.1897delC (p.Leu633Terfs) deletion Likely pathogenic rs863224858 GRCh37 Chromosome 1, 16382221: 16382221
13 CLCNKB NM_000085.4(CLCNKB): c.1897delC (p.Leu633Terfs) deletion Likely pathogenic rs863224858 GRCh38 Chromosome 1, 16055726: 16055726
14 CLCNKB NM_000085.4(CLCNKB): c.1381dupA (p.Ile461Asnfs) duplication Pathogenic rs1057516207 GRCh38 Chromosome 1, 16051793: 16051793
15 CLCNKB NM_000085.4(CLCNKB): c.1381dupA (p.Ile461Asnfs) duplication Pathogenic rs1057516207 GRCh37 Chromosome 1, 16378288: 16378288

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 10.48 BSND 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 15)
# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.83 ATP6V0A4 CLCNKB KCNJ1 SLC12A1 SLC12A3
2 cell volume homeostasis GO:0006884 9.55 SLC12A1 SLC12A3
3 regulation of type I interferon production GO:0032479 9.54 DDX41 TBK1
4 purine ribonucleoside monophosphate biosynthetic process GO:0009168 9.52 IMPDH1 IMPDH2
5 purine nucleotide biosynthetic process GO:0006164 9.51 IMPDH1 IMPDH2
6 potassium ion homeostasis GO:0055075 9.49 SLC12A1 SLC12A3
7 sodium ion homeostasis GO:0055078 9.48 SLC12A1 SLC12A3
8 GTP biosynthetic process GO:0006183 9.46 IMPDH1 IMPDH2
9 potassium ion import GO:0010107 9.43 KCNJ1 SLC12A1 SLC12A3
10 chloride ion homeostasis GO:0055064 9.4 SLC12A1 SLC12A3
11 lymphocyte proliferation GO:0046651 9.37 IMPDH1 IMPDH2
12 ion transmembrane transport GO:0034220 9.35 ATP6V0A4 BSND CLCNKB KCNJ1 SLC12A1
13 excretion GO:0007588 9.33 ATP6V0A4 CLCNKB KCNJ1
14 GMP biosynthetic process GO:0006177 9.32 IMPDH1 IMPDH2
15 chloride transmembrane transport GO:1902476 8.92 BSND 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 voltage-gated chloride channel activity GO:0005247 9.4 BSND CLCNKB
2 potassium:chloride symporter activity GO:0015379 9.37 SLC12A1 SLC12A3
3 cation:chloride symporter activity GO:0015377 9.32 SLC12A1 SLC12A3
4 sodium ion transmembrane transporter activity GO:0015081 9.26 SLC12A1 SLC12A3
5 IMP dehydrogenase activity GO:0003938 9.16 IMPDH1 IMPDH2
6 sodium:potassium:chloride symporter activity GO:0008511 8.96 SLC12A1 SLC12A3
7 sodium:chloride symporter activity GO:0015378 8.62 SLC12A1 SLC12A3

Sources for Bartter Syndrome, Type 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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