MCID: BRT042
MIFTS: 41

Bartter Syndrome, Type 3

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

Aliases & Classifications for Bartter Syndrome, Type 3

MalaCards integrated aliases for Bartter Syndrome, Type 3:

Name: Bartter Syndrome, Type 3 53 13 69
Bartter Syndrome Type 3 12 49 55 28
Classic Bartter Syndrome 12 55 71
Barts3 53 12 71
Bartter Syndrome, Classic 53 51
Bartter Disease Type 3 12 14
Bartter Syndrome Type Iii 55
Bartter Syndrome Classic 49
Adult Bartter Syndrome 55
Bartter Syndrome 3 71

Characteristics:

Orphanet epidemiological data:

55
classic bartter syndrome
Inheritance: Autosomal recessive; Age of onset: Adolescent,Adult,Childhood,Infancy;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
variable age of onset
clinical variation


HPO:

31
bartter syndrome, type 3:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Rare renal diseases


External Ids:

OMIM 53 607364
Disease Ontology 12 DOID:0110144
ICD10 32 E26.8
Orphanet 55 ORPHA93605
UMLS via Orphanet 70 C1846343
ICD10 via Orphanet 33 E26.8
MeSH 41 D001477
UMLS 69 C1846343

Summaries for Bartter Syndrome, Type 3

NIH Rare Diseases : 49 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. Last updated: 9/10/2014

MalaCards based summary : Bartter Syndrome, Type 3, also known as bartter syndrome type 3, is related to gitelman syndrome and bartter disease, and has symptoms including polyuria, generalized muscle weakness and hypotension. 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 cardiovascular system and homeostasis/metabolism

OMIM : 53 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 : 71 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.

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.

Related Diseases for Bartter Syndrome, Type 3

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:

53
Genitourinary Kidneys:
polyuria
renal salt wasting
renal potassium wasting
impaired reabsorption of chloride
nephrocalcinosis is absent

Metabolic Features:
dehydration
hypokalemic metabolic alkalosis

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

Cardiovascular Vascular:
low blood pressure

Muscle Soft Tissue:
generalized muscle weakness

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

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:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 polyuria 31 HP:0000103
2 generalized muscle weakness 31 HP:0003324
3 hypotension 31 HP:0002615
4 dehydration 31 HP:0001944
5 hypokalemia 31 HP:0002900
6 abnormality of the retinal vasculature 31 HP:0008046
7 hyperaldosteronism 31 HP:0000859
8 renal salt wasting 31 HP:0000127
9 increased circulating renin level 31 HP:0000848
10 hypocalciuria 31 occasional (7.5%) HP:0003127
11 increased urinary potassium 31 HP:0003081
12 hypokalemic metabolic alkalosis 31 HP:0001960
13 renal potassium wasting 31 HP:0000128
14 hyperactive renin-angiotensin system 31 HP:0000841
15 impaired reabsorption of chloride 31 HP:0005579
16 abnormal choroid morphology 31 HP:0000610
17 hyperchloriduria 31 HP:0002914
18 abnormal sclera morphology 31 HP:0000591

UMLS symptoms related to Bartter Syndrome, Type 3:


generalized muscle weakness, polyuria

MGI Mouse Phenotypes related to Bartter Syndrome, Type 3:

43
# 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 ATP6V0A4 BSND CLCNKB KCNJ1 PTGES REN
3 renal/urinary system MP:0005367 9.23 TBK1 ATP6V0A4 BSND 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 28 CLCNKB

Anatomical Context for Bartter Syndrome, Type 3

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

38
Kidney, Testes, 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:

71
# 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
# 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.610G> A (p.Ala204Thr) single nucleotide variant Pathogenic rs121909132 GRCh37 Chromosome 1, 16375032: 16375032
3 CLCNKB NM_000085.4(CLCNKB): c.1046C> A (p.Ala349Asp) single nucleotide variant Pathogenic rs121909134 GRCh37 Chromosome 1, 16377088: 16377088
4 CLCNKB NM_000085.4(CLCNKB): c.1294T> C (p.Tyr432His) single nucleotide variant Pathogenic rs121909135 GRCh37 Chromosome 1, 16378039: 16378039
5 CLCNKB CLCNKB, DEL deletion Pathogenic
6 CLCNKB CLCNKB, IVS7AS, A-G, -2 single nucleotide variant Pathogenic
7 CLCNKB CLCNKB, DEL deletion Pathogenic
8 CLCNKB NM_000085.4(CLCNKB): c.1897delC (p.Leu633Terfs) deletion Likely pathogenic rs863224858 GRCh37 Chromosome 1, 16382221: 16382221
9 CLCNKB NM_000085.4(CLCNKB): c.1381dupA (p.Ile461Asnfs) duplication Pathogenic rs1057516207 GRCh38 Chromosome 1, 16051793: 16051793

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 11)
# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.8 ATP6V0A4 CLCNKB KCNJ1 SLC12A1 SLC12A3
2 ion transmembrane transport GO:0034220 9.62 ATP6V0A4 BSND CLCNKB SLC12A1
3 regulation of anion transmembrane transport GO:1903959 9.49 BSND CLCNKB
4 regulation of type I interferon production GO:0032479 9.48 DDX41 TBK1
5 purine nucleotide biosynthetic process GO:0006164 9.46 IMPDH1 IMPDH2
6 purine ribonucleoside monophosphate biosynthetic process GO:0009168 9.43 IMPDH1 IMPDH2
7 GTP biosynthetic process GO:0006183 9.37 IMPDH1 IMPDH2
8 excretion GO:0007588 9.33 ATP6V0A4 CLCNKB KCNJ1
9 lymphocyte proliferation GO:0046651 9.26 IMPDH1 IMPDH2
10 GMP biosynthetic process GO:0006177 8.96 IMPDH1 IMPDH2
11 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 9.16 BSND CLCNKB
2 cation:chloride symporter activity GO:0015377 8.96 SLC12A1 SLC12A3
3 IMP dehydrogenase activity GO:0003938 8.62 IMPDH1 IMPDH2

Sources for Bartter Syndrome, Type 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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