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Bartter syndrome

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Synonyms and keywords: Salt-wasting Renal Tubular Disorder; Hyperprostaglandin E syndrome; juxtaglomerular hyperplasia with secondary aldosteronism; Barter disease; Barter’s disease; Bartter disease; Bartter’s disease Hypokalemic Metabolic Alkalosis

Overview

Overview

Main article:Bartter syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Overview

Bartter syndrome was first discovered by Bartter et al.and introduced in a seminal paper in the December issue of the American Journal of Medicine in 1962. Authors in the paper reported two pediatric patients with growth and developmental delay associated with hypokalemic alkalosis and normal blood pressure despite high aldosterone production. The syndrome named after Bartter. This disease was observed in children as well as in adults, females as well as males.Authors described in the paper that this disease is characterized by hypokalemia, metabolic alkalosis, hyperreninemia, secondary hyperaldosteronism, and normal blood pressure.Bartter Syndrome can be classified into five different types based on genotype. Bartter syndrome can result from homozygous or mixed heterozygous mutations in any of the genes. Thus, affecting the function of genes responsible for synthesis or membrane insertion of the transporters in the ascending limb of the loop of Henle. Bartter syndrome types 1, 2, and 4 present at a younger age. They present with symptoms, often quite severe in the neonatal period. Bartter syndrome type 3 also called classic Bartter syndrome present later in life and maybe sporadically asymptomatic or mildly symptomatic. The thick ascending limb of the loop of Henle is not permeable to water and reabsorbs a large proportion of the filtered sodium chloride as shown in the figure, which leads to interstitial hypertonicity that powers the countercurrent exchange and urinary concentration mechanisms. In case of impairment of this function, a major loss of water and sodium occurs, as seen with loop diuretics.Bartter syndrome is a renal tubular salt-wasting disorder in which the kidneys cannot reabsorb sodium and chloride in the thick ascending limb of the loop of Henle. Impairment of sodium and chloride reabsorption is the primary defect in the Bartter syndrome that initiates the cascade. This leads to increased delivery of salt to the distal tubules and excessive salt and water loss from the body. The resultant volume depletion causes activation of the renin-angiotensin-aldosterone system (RAAS) and subsequent secondary hyperaldosteronism. Long-term stimulation causes hyperplasia of the juxtaglomerular apparatus and elevates renin levels. Excessive distal delivery of sodium follows by sodium (Na) reabsorption in the distal convoluted tubule. Na reabsorption exchange with the secretion of positively charged potassium or hydrogen ion and leads to increased loss of potassium (K+) in urine and increased hydrogen (H+) secretion. Decreased chloride (Cl-) reabsorption decreases the exchange with bicarbonate (HCO3-). Thus, increased bicarbonate retention and hypokalemia result in metabolic alkalosis. Calcium and magnesium reabsorb in the ascending limb of the loop of Henle as a result of a positive electrochemical gradient in the lumen created by the back leak of K+ ion in the lumen, drives passive paracellular sodium, calcium, and magnesium reabsorption as shown in the figure. The defective sodium chloride transport in the ascending limb of the loop of Henle associated with Bartter syndrome leads to the impaired electrochemical gradient leading to increased urinary loss of calcium and magnesium. This leads to the development of nephrocalcinosis in Bartter syndrome. Bartter syndrome can be caused by mutations in at least five genes. Mutations in the SLC12A1 gene cause type I. Type II results from mutations in the KCNJ1 gene. Mutations in the CLCNKB gene are responsible for type III. Type IV can result from mutations in the BSND gene or from a combination of mutations in the CLCNKA and CLCNKB genes as shown in the table. Aminoglycoside can induce Bartter syndrome presenting with severe hypokalemia, metabolic alkalosis, and profound systemic manifestations. Bartter syndrome diagnosis should be differentiated from other diseases manifesting with hypokalemia and hypochloremic metabolic alkalosis such as Gitelman syndrome, EAST syndrome also is known as SeSAME syndrome, Diuretic abuse, cyclical vomiting, Hyperprostaglandin E syndrome(HPS), Familial hypomagnesemia, cystic fibrosis, Gullner syndrome, Mineralocorticoid excess, Activating mutation of the calcium-sensing receptor (CaSR) gene, Hypomagnesemia is often associated with hypokalemia, hypocalcemia, and metabolic alkalosis, Congenital chloride diarrhea, Hypochloremic alkalosis and Hypokalemia. Prolonged hypokalemia can lead to impaired ability of kidneys to concentrate urine, increased bicarbonate reabsorption. The prevalence of Barter Syndrome is approximately 1 in 1,000,000 individuals. The annual incidence of the syndrome has been estimated at 1.2 per million people. According to a review of twenty-eight patients with Bartter syndrome during the years 1964-1986 who were followed for an average of 10 years, their mean age at the time of diagnosis was 32.9 years. These patients were observed to have short stature than normal subjects. Bartter syndrome usually occurs in childhood. Bartter syndrome type I and type II are salt-wasting renal tubular disorders that are clinically characterized by polyhydramnios leading to premature delivery, marked polyuria, and a tendency towards nephrocalcinosis. Common complications of Bartter syndrome include Gallstones, Rhabdomyolysis, Prolonged QT interval, Life-threatening arrhythmia, Syncope, Sudden death, weakening of the bones and Renal failure. The limited prognostic information available suggests that early diagnosis and appropriate treatment of infants and young children with classic Bartter Syndrome (type 3) may improve growth and perhaps neuro-intellectual development. On the other hand, sustained hypokalemia and hyperreninemia can cause progressive tubulointerstitial nephritis, resulting in end-stage renal disease (Kidney failure). With the early treatment of the electrolyte imbalances, the prognosis for patients with Classic Bartter Syndrome is good. Patients with Bartter syndrome type I and II tend to present a satisfactory prognosis after a median follow-up of more than 10 years. Bartter syndrome is an autosomal recessive disorder that often presents in childhood and may be associated with stunted growth, mental retardation, hypokalemia, metabolic alkalosis, polyuria and polydipsia, normal to increased urinary calcium excretion, normal or mildly decreased serum magnesium concentration, hypophosphatemia and hypercalciuria. Laboratory findings such as Hypokalemia, Metabolic alkalosis, Elevated plasma renin and aldosterone, Elevated urine potassium and chloride, Low serum and urine magnesium levels. Abdominal radiographs and intravenous pyelograms (IVPs) can be done to document nephrocalcinosis. Polyhydramnios and intrauterine growth retardation are seen on ultrasound with the neonatal Barrter syndrome. There are no echocardiographic findings associated with Bartter syndrome. Genetic analysis is required to make an accurate diagnosis. Amniotic fluid chloride concentration ranged from 114 to 123 mEq/L has been reported in four newborns Bartter syndrome patients. In Bartter syndrome, a biopsy of the kidney typically shows redundant growth of kidney cells called the juxtaglomerular apparatus. However, this is not found in all patients, especially in young children. Prostaglandin synthetase inhibitors suppress the production of prostaglandin. Potassium chloride supplements are given for hypokalemia. Spironolactone, Amiloride, Triamterene, Angiotensin-converting enzyme (ACE) inhibitors, Nonsteroidal drug anti-inflammatory drugs (NSAID) are given to patients for the treatment of Bartter syndrome. Growth hormone (GH) is given for growth retardation. Calcium or magnesium supplements are given for muscle spasm and tetany. Bilateral nephrectomy and kidney transplantation have been performed successfully, in two patients with severe neonatal Bartter syndrome.

Historical Perspective

Bartter syndrome was first discovered by Bartter et al.and introduced in a seminal paper in the December issue of the American Journal of Medicine in 1962. Authors in the paper reported two pediatric patients with growth and developmental delay associated with hypokalemic alkalosis and normal blood pressure despite high aldosterone production. The syndrome named after Bartter. This disease was observed in children as well as in adults, females as well as males.Authors described in the paper that this disease is characterized by hypokalemia, metabolic alkalosis, hyperreninemia, secondary hyperaldosteronism, and normal blood pressure.

Classification

Bartter Syndrome can be classified into five different types based on genotype. Bartter syndrome can result from homozygous or mixed heterozygous mutations in any of the genes. Thus, affecting the function of genes responsible for synthesis or membrane insertion of the transporters in the ascending limb of the loop of Henle.

Bartter syndrome types 1, 2, and 4 present at a younger age. They present with symptoms, often quite severe in the neonatal period. Bartter syndrome type 3 also called classic Bartter syndrome present later in life and maybe sporadically asymptomatic or mildly symptomatic.

Pathophysiology

The thick ascending limb of the loop of Henle is not permeable to water and reabsorbs a large proportion of the filtered sodium chloride as shown in the figure, which leads to interstitial hypertonicity that powers the countercurrent exchange and urinary concentration mechanisms. In case of impairment of this function, a major loss of water and sodium occurs, as seen with loop diuretics.Bartter syndrome is a renal tubular salt-wasting disorder in which the kidneys cannot reabsorb sodium and chloride in the thick ascending limb of the loop of Henle. Impairment of sodium and chloride reabsorption is the primary defect in the Bartter syndrome that initiates the cascade. This leads to increased delivery of salt to the distal tubules and excessive salt and water loss from the body. The resultant volume depletion causes activation of the renin-angiotensin-aldosterone system (RAAS) and subsequent secondary hyperaldosteronism. Long-term stimulation causes hyperplasia of the juxtaglomerular apparatus and elevates renin levels. Excessive distal delivery of sodium follows by sodium (Na) reabsorption in the distal convoluted tubule. Na reabsorption exchange with the secretion of positively charged potassium or hydrogen ion and leads to increased loss of potassium (K+) in urine and increased hydrogen (H+) secretion. Decreased chloride (Cl-) reabsorption decreases the exchange with bicarbonate (HCO3-). Thus, increased bicarbonate retention and hypokalemia result in metabolic alkalosis. Calcium and magnesium reabsorb in the ascending limb of the loop of Henle as a result of a positive electrochemical gradient in the lumen created by the back leak of K+ ion in the lumen, drives passive paracellular sodium, calcium, and magnesium reabsorption as shown in the figure. The defective sodium chloride transport in the ascending limb of the loop of Henle associated with Bartter syndrome leads to the impaired electrochemical gradient leading to increased urinary loss of calcium and magnesium. This leads to the development of nephrocalcinosis in Bartter syndrome.

Causes

Bartter syndrome can be caused by mutations in at least five genes. Mutations in the SLC12A1 gene cause type I. Type II results from mutations in the KCNJ1 gene. Mutations in the CLCNKB gene are responsible for type III. Type IV can result from mutations in the BSND gene or from a combination of mutations in the CLCNKA and CLCNKB genes as shown in the table. Aminoglycoside can induce Bartter syndrome presenting with severe hypokalemia, metabolic alkalosis, and profound systemic manifestations.

Differentiating Bartter syndrome from Other Diseases

Bartter syndrome diagnosis should be differentiated from other diseases manifesting with hypokalemia and hypochloremic metabolic alkalosis such as Gitelman syndrome, EAST syndrome also is known as SeSAME syndrome, Diuretic abuse, cyclical vomiting, Hyperprostaglandin E syndrome(HPS), Familial hypomagnesemia, cystic fibrosis, Gullner syndrome, Mineralocorticoid excess, Activating mutation of the calcium-sensing receptor (CaSR) gene, Hypomagnesemia is often associated with hypokalemia, hypocalcemia, and metabolic alkalosis, Congenital chloride diarrhea, Hypochloremic alkalosis and Hypokalemia. Prolonged hypokalemia can lead to impaired ability of kidneys to concentrate urine, increased bicarbonate reabsorption.

Epidemiology and Demographics

The prevalence of Barter Syndrome is approximately 1 in 1,000,000 individuals. The annual incidence of the syndrome has been estimated at 1.2 per million people. According to a review of twenty-eight patients with Bartter syndrome during the years 1964-1986 who were followed for an average of 10 years, their mean age at the time of diagnosis was 32.9 years. These patients were observed to have short stature than normal subjects.

Risk Factors

Anyone with a family history of Bartter syndrome is at risk.

Screening

Genetic screening for Bartter syndrome mutated genes can be performed among individuals with unexplained hypertension and hypokalemia.

Natural History, Complications, and Prognosis

Bartter syndrome usually occurs in childhood. Bartter syndrome type I and type II are salt-wasting renal tubular disorders that are clinically characterized by polyhydramnios leading to premature delivery, marked polyuria, and a tendency towards nephrocalcinosis. Common complications of Bartter syndrome include Gallstones, Rhabdomyolysis, Prolonged QT interval, Life-threatening arrhythmia, Syncope, Sudden death, weakening of the bones and Renal failure. The limited prognostic information available suggests that early diagnosis and appropriate treatment of infants and young children with classic Bartter Syndrome (type 3) may improve growth and perhaps neuro-intellectual development. On the other hand, sustained hypokalemia and hyperreninemia can cause progressive tubulointerstitial nephritis, resulting in end-stage renal disease (Kidney failure). With the early treatment of the electrolyte imbalances, the prognosis for patients with Classic Bartter Syndrome is good. Patients with Bartter syndrome type I and II tend to present a satisfactory prognosis after a median follow-up of more than 10 years.

Diagnosis

History and Symptoms

Bartter syndrome is an autosomal recessive disorder that often presents in childhood and may be associated with stunted growth, mental retardation, hypokalemia, metabolic alkalosis, polyuria and polydipsia, normal to increased urinary calcium excretion, normal or mildly decreased serum magnesium concentration, hypophosphatemia and hypercalciuria.

Physical Examination

Physical examination findings include Prominent forehead, a large head, triangular facies with the drooping mouth, and large eyes and pinnae, low blood pressure, dehydrated, stunted growth, and muscle weakness.

Laboratory Findings

Laboratory findings such as Hypokalemia, Metabolic alkalosis, Elevated plasma renin and aldosterone, Elevated urine potassium and chloride, Low serum and urine magnesium levels.

Electrocardiogram

Hypokalemia in Bartter syndrome can lead to prolonged QT interval, life-threatening arrhythmia, syncope, and sudden death.

X-ray

Abdominal radiographs and intravenous pyelograms (IVPs) can be done to document nephrocalcinosis.

Echocardiography and Ultrasound

Polyhydramnios and intrauterine growth retardation are seen on ultrasound with the neonatal Barrter syndrome. There are no echocardiographic findings associated with Bartter syndrome.

CT scan

Spiral CT scan can be performed to look for nephrocalcinosis in Bartter syndrome.

MRI

There are no MRI findings associated with Bartter syndrome.

Other Diagnostic Studies

Genetic analysis is required to make an accurate diagnosis. Amniotic fluid chloride concentration ranged from 114 to 123 mEq/L has been reported in four newborns Bartter syndrome patients. In Bartter syndrome, a biopsy of the kidney typically shows redundant growth of kidney cells called the juxtaglomerular apparatus. However, this is not found in all patients, especially in young children

Treatment

Medical Therapy

Prostaglandin synthetase inhibitors suppress the production of prostaglandin. Potassium chloride supplements are given for hypokalemia. Spironolactone, Amiloride, Triamterene, Angiotensin-converting enzyme (ACE) inhibitors, Nonsteroidal drug anti-inflammatory drugs (NSAID) are given to patients for the treatment of Bartter syndrome. Growth hormone (GH) is given for growth retardation. Calcium or magnesium supplements are given for muscle spasm and tetany.

Surgery

Bilateral nephrectomy and kidney transplantation have been performed successfully, in two patients with severe neonatal Bartter syndrome.

Future or Investigational therapies

Experimental treatments that are being examined depend on the revelation that a few mutations causing Bartter syndrome create carriers with normal function. In any case, the mutations bring about the sequestration of these carriers inside intracellular compartments with the goal that they neglect to effectively embed into the suitable cell membrane. When these proteins can be effectively embedded into the cell membrane, they can become functional and correct the defect. The delivery and insertion of these fully or partially functional proteins into the cell membrane and partially rescue sodium chloride reabsorption can be improved by the utilization of the molecular chaperones, such as 4-phenylbutyrate.

Primary Prevention

There is no primary prevention associated with Bartter syndrome.

Secondary Prevention

Careful monitoring is required since NSAIDs can have significant adverse effects including renal and gastrointestinal toxicity.

References


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Historical Perspective

Historical Perspective

Main article: Bartter syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Overview

Bartter syndrome was first discovered by Bartter et al.and introduced in a seminal paper in the December issue of the American Journal of Medicine in 1962. Authors in the paper reported two pediatric patients with growth and developmental delay associated with hypokalemic alkalosis and normal blood pressure despite high aldosterone production. The syndrome named after Bartter. This disease was observed in children as well as in adults, females as well as males.Authors described in the paper that this disease is characterized by hypokalemia, metabolic alkalosis, hyperreninemia, secondary hyperaldosteronism, and normal blood pressure.

Historical Perspective

References

  1. ↑ Proesmans W (2006). “Threading through the mizmaze of Bartter syndrome”. Pediatr Nephrol. 21 (7): 896–902. doi:10.1007/s00467-006-0113-7. PMID 16773399.
  2. ↑ BARTTER FC, PRONOVE P, GILL JR, MACCARDLE RC (1962). “Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. A new syndrome”. Am J Med. 33: 811–28. doi:10.1016/0002-9343(62)90214-0. PMID 13969763.
  3. ↑ Fichman MP, Telfer N, Zia P, Speckart P, Golub M, Rude R (1976). “Role of prostaglandins in the pathogenesis of Bartter’s syndrome”. Am J Med. 60 (6): 785–97. doi:10.1016/0002-9343(76)90892-5. PMID 798488.
  4. ↑ “www.kidney-international.org”.
  5. ↑ Gill JR, Frölich JC, Bowden RE, Taylor AA, Keiser HR, Seyberth HW; et al. (1976). “Bartter’s syndrome: a disorder characterized by high urinary prostaglandins and a dependence of hyperreninemia on prostaglandin synthesis”. Am J Med. 61 (1): 43–51. doi:10.1016/0002-9343(76)90029-2. PMID 820194.
  6. ↑ Güllner HG, Cerletti C, Bartter FC, Smith JB, Gill JR (1979). “Prostacyclin overproduction in Bartter’s syndrome”. Lancet. 2 (8146): 767–9. doi:10.1016/s0140-6736(79)92116-0. PMID 90861.
  7. ↑ Davison AG, Snodgrass GJ (1983). “Cystic fibrosis mimicking Bartter’s syndrome”. Acta Paediatr Scand. 72 (5): 781–3. doi:10.1111/j.1651-2227.1983.tb09814.x. PMID 6356778.


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Classification

Classification

Main article: Bartter syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Overview

Bartter Syndrome can be classified into five different types based on genotype. Bartter syndrome can result from homozygous or mixed heterozygous mutations in any of the genes. Thus, affecting the function of genes responsible for synthesis or membrane insertion of the transporters in the ascending limb of the loop of Henle. Mutation in NKCC2 gene results in impairment of sodium-potassium-chloride. cotransporter (Na-K-2Cl) in the apical membrane. Mutation in ROMK gene results in defective functioning of the luminal potassium channel. Mutation in the ClC-Kb gene results in the impairment of the basolateral chloride channel. Defects that reduce the activity of both ClC-Ka and ClC-Kb cause Bartter syndrome associated with sensorineural deafness (types IV and IVb). Type 5 Bartter syndrome results from a gain-of-function mutation in the Ca-sensing receptor (CaSR). A gain-of-function mutation in CaSR in the basolateral membrane of the thick ascending limb enhances the function of this receptor. This results in hypocalcemia and impairs sodium chloride transport. Bartter syndrome types 1, 2, and 4 present at a younger age. They present with symptoms, often quite severe in the neonatal period. Bartter syndrome type 3 also called classic Bartter syndrome present later in life and maybe sporadically asymptomatic or mildly symptomatic.

Classification

  • Bartter Syndrome type 2
  • Bartter Syndrome type 3
  • Bartter Syndrome type 4
  • Bartter Syndrome type 5
Classification of Bartter syndrome on the basis of both genotype and phenotype[11][12]
Disorder Gene affected Gene product Clinical presentation (phenotype)
Bartter syndrome type I SLC12A1 NKCC2 Antenatal Bartter syndrome (hyperprostaglandin E syndrome)
Bartter syndrome type II KCNJ1 ROMK Antenatal Bartter syndrome
Bartter syndrome type III ClC-Kb CLC-Kb Hypochloremia, mild hypomagnesemia, failure to thrive in infancy
Bartter syndrome type IVA BSND Barttin (B-subunit of CLC-Ka and CLC-Kb) Antenatal Bartter syndrome (hyperprostaglandin E syndrome) and sensorineural deafness
Bartter syndrome type IVB ClC-Ka and ClC-Kb CLC-Ka and CLC-Kb Antenatal Bartter syndrome (hyperprostaglandin E syndrome) and sensorineural deafness
Bartter syndrome type V CaSR gene CaSR Bartter syndrome with hypocalcemia



  • Bartter syndrome types 1, 2, and 4 present at a younger age. They present with symptoms, often quite severe in the neonatal period.
  • Bartter syndrome type 3 also called classic Bartter syndrome present later in life and maybe sporadically asymptomatic or mildly symptomatic.[13]

References

  1. ↑ 1.0 1.1 Simon DB, Karet FE, Hamdan JM, DiPietro A, Sanjad SA, Lifton RP (1996). “Bartter’s syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2”. Nat Genet. 13 (2): 183–8. doi:10.1038/ng0696-183. PMID 8640224.
  2. ↑ 2.0 2.1 Simon DB, Karet FE, Rodriguez-Soriano J, Hamdan JH, DiPietro A, Trachtman H; et al. (1996). “Genetic heterogeneity of Bartter’s syndrome revealed by mutations in the K+ channel, ROMK”. Nat Genet. 14 (2): 152–6. doi:10.1038/ng1096-152. PMID 8841184.
  3. ↑ 3.0 3.1 Lorenz JN, Baird NR, Judd LM, Noonan WT, Andringa A, Doetschman T; et al. (2002). “Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter’s syndrome”. J Biol Chem. 277 (40): 37871–80. doi:10.1074/jbc.M205627200. PMID 12122007.
  4. ↑ 4.0 4.1 Simon DB, Bindra RS, Mansfield TA, Nelson-Williams C, Mendonca E, Stone R; et al. (1997). “Mutations in the chloride channel gene, CLCNKB, cause Bartter’s syndrome type III”. Nat Genet. 17 (2): 171–8. doi:10.1038/ng1097-171. PMID 9326936.
  5. ↑ 5.0 5.1 Konrad M, Vollmer M, Lemmink HH, van den Heuvel LP, Jeck N, Vargas-Poussou R; et al. (2000). “Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome”. J Am Soc Nephrol. 11 (8): 1449–59. PMID 10906158.
  6. ↑ 6.0 6.1 Krämer BK, Bergler T, Stoelcker B, Waldegger S (2008). “Mechanisms of Disease: the kidney-specific chloride channels ClCKA and ClCKB, the Barttin subunit, and their clinical relevance”. Nat Clin Pract Nephrol. 4 (1): 38–46. doi:10.1038/ncpneph0689. PMID 18094726.
  7. ↑ Janssen AG, Scholl U, Domeyer C, Nothmann D, Leinenweber A, Fahlke C (2009). “Disease-causing dysfunctions of barttin in Bartter syndrome type IV”. J Am Soc Nephrol. 20 (1): 145–53. doi:10.1681/ASN.2008010102. PMC 2615720. PMID 18776122.
  8. ↑ Kitanaka S, Sato U, Maruyama K, Igarashi T (2006). “A compound heterozygous mutation in the BSND gene detected in Bartter syndrome type IV”. Pediatr Nephrol. 21 (2): 190–3. doi:10.1007/s00467-005-2091-6. PMID 16328537.
  9. ↑ Hebert SC (1996). “Extracellular calcium-sensing receptor: implications for calcium and magnesium handling in the kidney”. Kidney Int. 50 (6): 2129–39. doi:10.1038/ki.1996.539. PMID 8943500.
  10. ↑ Watanabe S, Fukumoto S, Chang H, Takeuchi Y, Hasegawa Y, Okazaki R; et al. (2002). “Association between activating mutations of calcium-sensing receptor and Bartter’s syndrome”. Lancet. 360 (9334): 692–4. doi:10.1016/S0140-6736(02)09842-2. PMID 12241879.
  11. ↑ Seyberth HW (2008). “An improved terminology and classification of Bartter-like syndromes”. Nat Clin Pract Nephrol. 4 (10): 560–7. doi:10.1038/ncpneph0912. PMID 18695706.
  12. ↑ Al Shibli A, Narchi H (2015). “Bartter and Gitelman syndromes: Spectrum of clinical manifestations caused by different mutations”. World J Methodol. 5 (2): 55–61. doi:10.5662/wjm.v5.i2.55. PMC 4482822. PMID 26140272.
  13. ↑ Fremont OT, Chan JC (2012). “Understanding Bartter syndrome and Gitelman syndrome”. World J Pediatr. 8 (1): 25–30. doi:10.1007/s12519-012-0333-9. PMID 22282380.
Pathophysiology

Pathophysiology

Main article: Bartter syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Overview

The thick ascending limb of the loop of Henle is not permeable to water and reabsorbs a large proportion of the filtered sodium chloride as shown in the figure, which leads to interstitial hypertonicity that powers the countercurrent exchange and urinary concentration mechanisms. In case of impairment of this function, a major loss of water and sodium occurs, as seen with loop diuretics.Bartter syndrome is a renal tubular salt-wasting disorder in which the kidneys cannot reabsorb sodium and chloride in the thick ascending limb of the loop of Henle. Impairment of sodium and chloride reabsorption is the primary defect in the Bartter syndrome that initiates the cascade. This leads to increased delivery of salt to the distal tubules and excessive salt and water loss from the body. The resultant volume depletion causes activation of the renin-angiotensin-aldosterone system (RAAS) and subsequent secondary hyperaldosteronism. Long-term stimulation causes hyperplasia of the juxtaglomerular apparatus and elevates renin levels. Excessive distal delivery of sodium follows by sodium (Na) reabsorption in the distal convoluted tubule. Na reabsorption exchange with the secretion of positively charged potassium or hydrogen ion and leads to increased loss of potassium (K+) in urine and increased hydrogen (H+) secretion. Decreased chloride (Cl-) reabsorption decreases the exchange with bicarbonate (HCO3-). Thus, increased bicarbonate retention and hypokalemia result in metabolic alkalosis. Calcium and magnesium reabsorb in the ascending limb of the loop of Henle as a result of a positive electrochemical gradient in the lumen created by the back leak of K+ ion in the lumen, drives passive paracellular sodium, calcium, and magnesium reabsorption as shown in the figure. The defective sodium chloride transport in the ascending limb of the loop of Henle associated with Bartter syndrome leads to the impaired electrochemical gradient leading to increased urinary loss of calcium and magnesium. This leads to the development of nephrocalcinosis in Bartter syndrome.

Pathophysiology



  • Cl-channel kidney B (ClC-Kb) is the primary channel in the basolateral membrane of thick ascending limb for chloride reabsorption. Another chloride channel, Cl-channel kidney A (ClC-Ka), may have excess usefulness.
  • Barttin is a small protein beta-subunit that collaborates with these chloride channels and enhances their functionality.
  • These chloride channels also play an important role in ion transport in the ear, accounting for the association between some genetic renal transport defects and deafness. Neurosensory deafness can be a rare complication of Bartter syndrome when it is caused by specific mutations.[7]
  • To browse the types of mutations responsible for different types of Bartter syndrome, click here.
  • Hypokalemia has three further direct sequelae—increased production of PGE2 by renal cells, increased production of PGI2 by blood vessels, and decreased production of aldosterone by the adrenals. The increase in PGE2 stimulates renin production, which in turn results in increased angiotensin II and stimulation of aldosterone production by the adrenal gland.[8]

References

  1. ↑ Seyberth HW, Schlingmann KP (2011). “Bartter- and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT defects”. Pediatr Nephrol. 26 (10): 1789–802. doi:10.1007/s00467-011-1871-4. PMC 3163795. PMID 21503667.
  2. ↑ Deschênes G, Fila M (2011). “Primary molecular disorders and secondary biological adaptations in bartter syndrome”. Int J Nephrol. 2011: 396209. doi:10.4061/2011/396209. PMC 3177086. PMID 21941653.
  3. ↑ BARTTER FC, PRONOVE P, GILL JR, MACCARDLE RC (1962). “Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. A new syndrome”. Am J Med. 33: 811–28. doi:10.1016/0002-9343(62)90214-0. PMID 13969763.
  4. ↑ Soylu Ustkoyuncu P, Nalcacioglu H, Bastug F, Yel S, Altuner Torun Y (2019). “Association of Mucopolysaccharidosis Type 4A and Bartter Syndrome”. Iran J Kidney Dis. 13 (1): 71–72. PMID 30851722.
  5. ↑ Al Shibli A, Narchi H (2015). “Bartter and Gitelman syndromes: Spectrum of clinical manifestations caused by different mutations”. World J Methodol. 5 (2): 55–61. doi:10.5662/wjm.v5.i2.55. PMC 4482822. PMID 26140272.
  6. ↑ Seyberth HW (2008). “An improved terminology and classification of Bartter-like syndromes”. Nat Clin Pract Nephrol. 4 (10): 560–7. doi:10.1038/ncpneph0912. PMID 18695706.
  7. ↑ Andrini O, Keck M, Briones R, Lourdel S, Vargas-Poussou R, Teulon J (2015). “ClC-K chloride channels: emerging pathophysiology of Bartter syndrome type 3”. Am J Physiol Renal Physiol. 308 (12): F1324–34. doi:10.1152/ajprenal.00004.2015. PMID 25810436.
  8. ↑ “www.kidney-international.org”.


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Causes

Causes

Main article: Bartter syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Overview

Bartter syndrome can be caused by mutations in at least five genes. Mutations in the SLC12A1 gene cause type I. Type II results from mutations in the KCNJ1 gene. Mutations in the CLCNKB gene are responsible for type III. Type IV can result from mutations in the BSND gene or from a combination of mutations in the CLCNKA and CLCNKB genes as shown in the table. Aminoglycoside can induce Bartter syndrome presenting with severe hypokalemia, metabolic alkalosis, and profound systemic manifestations.

Causes

  • Bartter syndrome can be caused by mutations in at least five genes.
  • Mutations in the SLC12A1 gene cause type I. Type II results from mutations in the KCNJ1 gene. Mutations in the CLCNKB gene are responsible for type III. Type IV can result from mutations in the BSND gene or from a combination of mutations in the CLCNKA and CLCNKB genes as shown in the table.
  • The genes associated with Bartter syndrome play important roles in normal kidney function. The proteins produced from these genes are involved in the kidneys’ reabsorption of salt.
  • Mutations in any of the five genes impair the kidneys’ ability to reabsorb salt, leading to the loss of excess salt in the urine (salt wasting). Abnormalities of salt transport also affect the reabsorption of other charged atoms (ions), including potassium and calcium. The resulting imbalance of ions in the body leads to the major features of Bartter syndrome.[1]
Classification of Bartter syndrome on the basis of both genotype and phenotype[2][3]
Disorder Gene affected Gene product Clinical presentation (phenotype)
Bartter syndrome type I SLC12A1 NKCC2 Antenatal Bartter syndrome (hyperprostaglandin E syndrome)
Bartter syndrome type II KCNJ1 ROMK Antenatal Bartter syndrome
Bartter syndrome type III ClC-Kb CLC-Kb Hypochloremia, mild hypomagnesemia, failure to thrive in infancy
Bartter syndrome type IVA BSND Barttin (B-subunit of CLC-Ka and CLC-Kb) Antenatal Bartter syndrome (hyperprostaglandin E syndrome) and sensorineural deafness
Bartter syndrome type IVB ClC-Ka and ClC-Kb CLC-Ka and CLC-Kb Antenatal Bartter syndrome (hyperprostaglandin E syndrome) and sensorineural deafness
Bartter syndrome type V CaSR gene CaSR Bartter syndrome with hypocalcemia


References

  1. ↑ 1.0 1.1 “Bartter syndrome – Genetics Home Reference – NIH”.
  2. ↑ Seyberth HW (2008). “An improved terminology and classification of Bartter-like syndromes”. Nat Clin Pract Nephrol. 4 (10): 560–7. doi:10.1038/ncpneph0912. PMID 18695706.
  3. ↑ Al Shibli A, Narchi H (2015). “Bartter and Gitelman syndromes: Spectrum of clinical manifestations caused by different mutations”. World J Methodol. 5 (2): 55–61. doi:10.5662/wjm.v5.i2.55. PMC 4482822. PMID 26140272.
  4. ↑ McLarnon S, Holden D, Ward D, Jones M, Elliott A, Riccardi D (2002). “Aminoglycoside antibiotics induce pH-sensitive activation of the calcium-sensing receptor”. Biochem Biophys Res Commun. 297 (1): 71–7. doi:10.1016/s0006-291x(02)02133-2. PMID 12220510.


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Differentiating Bartter syndrome from other Diseases

Differentiating Bartter syndrome from other Diseases

Main article: Bartter syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Overview

Bartter syndrome diagnosis should be differentiated from other diseases manifesting with hypokalemia and hypochloremic metabolic alkalosis such as Gitelman syndrome, EAST syndrome also is known as SeSAME syndrome, Diuretic abuse, cyclical vomiting, Hyperprostaglandin E syndrome(HPS), Familial hypomagnesemia, cystic fibrosis, Gullner syndrome, Mineralocorticoid excess, Activating mutation of the calcium-sensing receptor (CaSR) gene, Hypomagnesemia is often associated with hypokalemia, hypocalcemia, and metabolic alkalosis, Congenital chloride diarrhea, Hypochloremic alkalosis and Hypokalemia. Prolonged hypokalemia can lead to impaired ability of kidneys to concentrate urine, increased bicarbonate reabsorption.

Differentiating Bartter syndrome from other Diseases

Bartter syndrome diagnosis should be differentiated from other diseases manifesting with hypokalemia and hypochloremic metabolic alkalosis.[1]

Disease Findings
Gitelman syndrome
EAST syndrome
Diuretic abuse
Cyclical vomiting
Hyperprostaglandin E syndrome
Familial hypomagnesemia with hypercalciuria/nephrocalcinosis
Cystic fibrosis
Gullner syndrome – Familial hypokalemic alkalosis with proximal tubulopathy
Mineralocorticoid excess
Activating mutations of the CaSR calcium-sensing receptor
  • Patients with activating mutation of the calcium-sensing receptor (CaSR) gene presents with potassium wasting, hypokalemia, and metabolic alkalosis, similar to Bartter syndrome.[26][27]
  • An activating (or gain-of-function) mutation of the calcium-sensing receptor (CaSR) gene impairs the calcium balance in the body and cause hypocalcemia.
  • Activating mutation in the receptor increases the threshold for the receptor to detect the low calcium level. This causes the parathyroid hormone (PTH) to not release at serum calcium level that normally signals PTH release.[28][29][30]
Hypomagnesemia
Congenital chloride diarrhea
Hypochloremic alkalosis
Hypokalemia

References

  1. ↑ Gitelman HJ, Graham JB, Welt LG (1966). “A new familial disorder characterized by hypokalemia and hypomagnesemia”. Trans Assoc Am Physicians. 79: 221–35. PMID 5929460.
  2. ↑ Scognamiglio R, Negut C, Calò LA (2007). “Aborted sudden cardiac death in two patients with Bartter’s/Gitelman’s syndromes”. Clin Nephrol. 67 (3): 193–7. doi:10.5414/cnp67193. PMID 17390745.
  3. ↑ Urbanová M, Reiterová J, Stěkrová J, Lněnička P, Ryšavá R (2011). “DNA analysis of renal electrolyte transporter genes among patients suffering from Bartter and Gitelman syndromes: summary of mutation screening”. Folia Biol (Praha). 57 (2): 65–73. PMID 21631963.
  4. ↑ Bockenhauer D, Feather S, Stanescu HC, Bandulik S, Zdebik AA, Reichold M; et al. (2009). “Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations”. N Engl J Med. 360 (19): 1960–70. doi:10.1056/NEJMoa0810276. PMC 3398803. PMID 19420365.
  5. ↑ Scholl UI, Choi M, Liu T, Ramaekers VT, Häusler MG, Grimmer J; et al. (2009). “Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10”. Proc Natl Acad Sci U S A. 106 (14): 5842–7. doi:10.1073/pnas.0901749106. PMC 2656559. PMID 19289823.
  6. ↑ Jamison RL, Ross JC, Kempson RL, Sufit CR, Parker TE (1982). “Surreptitious diuretic ingestion and pseudo-Bartter’s syndrome”. Am J Med. 73 (1): 142–7. doi:10.1016/0002-9343(82)90941-x. PMID 7091169.
  7. ↑ Colussi G, Rombolà G, Airaghi C, De Ferrari ME, Minetti L (1992). “Pseudo-Bartter’s syndrome from surreptitious diuretic intake: differential diagnosis with true Bartter’s syndrome”. Nephrol Dial Transplant. 7 (9): 896–901. doi:10.1093/ndt/7.9.896. PMID 1328936.
  8. ↑ Sasaki H, Kawasaki T, Yamamoto T, Ninomiya H, Ono J, Yamamoto T; et al. (1986). “[Pseudo-Bartter’s syndrome induced by surreptitious ingestion of furosemide to lose weight: a case report and possible pathophysiology]”. Nihon Naibunpi Gakkai Zasshi. 62 (8): 867–81. doi:10.1507/endocrine1927.62.8_867. PMID 3023152.
  9. ↑ D’Avanzo M, Santinelli R, Tolone C, Bettinelli A, Bianchetti MG (1995). “Concealed administration of frusemide simulating Bartter syndrome in a 4.5-year-old boy”. Pediatr Nephrol. 9 (6): 749–50. doi:10.1007/BF00868731. PMID 8747119.
  10. ↑ 10.0 10.1 Veldhuis JD, Bardin CW, Demers LM (1979). “Metabolic mimicry of Bartter’s syndrome by covert vomiting: utility of urinary chloride determinations”. Am J Med. 66 (2): 361–3. doi:10.1016/0002-9343(79)90566-7. PMID 425977.
  11. ↑ Cetinkaya M, Köksal N, Ozkan H, Dönmez O, Sağlam H, Kiriştioğlu I (2008). “Hyperprostaglandin E syndrome: use of indomethacin and steroid, and death due to necrotizing enterocolitis and sepsis”. Turk J Pediatr. 50 (4): 386–90. PMID 19014056.
  12. ↑ Praga M, Vara J, González-Parra E, Andrés A, Alamo C, Araque A; et al. (1995). “Familial hypomagnesemia with hypercalciuria and nephrocalcinosis”. Kidney Int. 47 (5): 1419–25. doi:10.1038/ki.1995.199. PMID 7637271.
  13. ↑ Nicholson JC, Jones CL, Powell HR, Walker RG, McCredie DA (1995). “Familial hypomagnesaemia–hypercalciuria leading to end-stage renal failure”. Pediatr Nephrol. 9 (1): 74–6. doi:10.1007/BF00858976. PMID 7742227.
  14. ↑ Benigno V, Canonica CS, Bettinelli A, von Vigier RO, Truttmann AC, Bianchetti MG (2000). “Hypomagnesaemia-hypercalciuria-nephrocalcinosis: a report of nine cases and a review”. Nephrol Dial Transplant. 15 (5): 605–10. doi:10.1093/ndt/15.5.605. PMID 10809799.
  15. ↑ Müller D, Kausalya PJ, Bockenhauer D, Thumfart J, Meij IC, Dillon MJ; et al. (2006). “Unusual clinical presentation and possible rescue of a novel claudin-16 mutation”. J Clin Endocrinol Metab. 91 (8): 3076–9. doi:10.1210/jc.2006-0200. PMID 16705067.
  16. ↑ Konrad M, Hou J, Weber S, Dötsch J, Kari JA, Seeman T; et al. (2008). “CLDN16 genotype predicts renal decline in familial hypomagnesemia with hypercalciuria and nephrocalcinosis”. J Am Soc Nephrol. 19 (1): 171–81. doi:10.1681/ASN.2007060709. PMC 2391030. PMID 18003771.
  17. ↑ Kose M, Pekcan S, Ozcelik U, Cobanoglu N, Yalcin E, Dogru D; et al. (2008). “An epidemic of pseudo-Bartter syndrome in cystic fibrosis patients”. Eur J Pediatr. 167 (1): 115–6. doi:10.1007/s00431-007-0413-3. PMID 17323076.
  18. ↑ Kennedy JD, Dinwiddie R, Daman-Willems C, Dillon MJ, Matthew DJ (1990). “Pseudo-Bartter’s syndrome in cystic fibrosis”. Arch Dis Child. 65 (7): 786–7. doi:10.1136/adc.65.7.786. PMC 1792454. PMID 2386386.
  19. ↑ Bates CM, Baum M, Quigley R (1997). “Cystic fibrosis presenting with hypokalemia and metabolic alkalosis in a previously healthy adolescent”. J Am Soc Nephrol. 8 (2): 352–5. PMID 9048354.
  20. ↑ Davé S, Honney S, Raymond J, Flume PA (2005). “An unusual presentation of cystic fibrosis in an adult”. Am J Kidney Dis. 45 (3): e41–4. doi:10.1053/j.ajkd.2004.11.009. PMID 15754262.
  21. ↑ Leoni GB, Pitzalis S, Podda R, Zanda M, Silvetti M, Caocci L; et al. (1995). “A specific cystic fibrosis mutation (T3381) associated with the phenotype of isolated hypotonic dehydration”. J Pediatr. 127 (2): 281–3. doi:10.1016/s0022-3476(95)70310-1. PMID 7543567.
  22. ↑ Güllner HG, Bartter FC, Gill JR, Dickman PS, Wilson CB, Tiwari JL (1983). “A sibship with hypokalemic alkalosis and renal proximal tubulopathy”. Arch Intern Med. 143 (8): 1534–40. doi:10.1001/archinte.1983.00350080040011. PMID 6347111.
  23. ↑ Morineau G, Sulmont V, Salomon R, Fiquet-Kempf B, Jeunemaître X, Nicod J; et al. (2006). “Apparent mineralocorticoid excess: report of six new cases and extensive personal experience”. J Am Soc Nephrol. 17 (11): 3176–84. doi:10.1681/ASN.2006060570. PMID 17035606.
  24. ↑ Dave-Sharma S, Wilson RC, Harbison MD, Newfield R, Azar MR, Krozowski ZS; et al. (1998). “Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess”. J Clin Endocrinol Metab. 83 (7): 2244–54. doi:10.1210/jcem.83.7.4986. PMID 9661590.
  25. ↑ Bockenhauer D, van’t Hoff W, Dattani M, Lehnhardt A, Subtirelu M, Hildebrandt F; et al. (2010). “Secondary nephrogenic diabetes insipidus as a complication of inherited renal diseases”. Nephron Physiol. 116 (4): p23–9. doi:10.1159/000320117. PMC 3896046. PMID 20733335.
  26. ↑ Watanabe S, Fukumoto S, Chang H, Takeuchi Y, Hasegawa Y, Okazaki R; et al. (2002). “Association between activating mutations of calcium-sensing receptor and Bartter’s syndrome”. Lancet. 360 (9334): 692–4. doi:10.1016/S0140-6736(02)09842-2. PMID 12241879.
  27. ↑ Konrad M, Weber S (2003). “Recent advances in molecular genetics of hereditary magnesium-losing disorders”. J Am Soc Nephrol. 14 (1): 249–60. doi:10.1097/01.asn.0000049161.60740.ce. PMID 12506158.
  28. ↑ Brown EM (2007). “Clinical lessons from the calcium-sensing receptor”. Nat Clin Pract Endocrinol Metab. 3 (2): 122–33. doi:10.1038/ncpendmet0388. PMID 17237839.
  29. ↑ Pollak MR, Brown EM, Estep HL, McLaine PN, Kifor O, Park J; et al. (1994). “Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation”. Nat Genet. 8 (3): 303–7. doi:10.1038/ng1194-303. PMID 7874174.
  30. ↑ D’Souza-Li L, Yang B, Canaff L, Bai M, Hanley DA, Bastepe M; et al. (2002). “Identification and functional characterization of novel calcium-sensing receptor mutations in familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia”. J Clin Endocrinol Metab. 87 (3): 1309–18. doi:10.1210/jcem.87.3.8280. PMID 11889203.
  31. ↑ Tong GM, Rude RK (2005). “Magnesium deficiency in critical illness”. J Intensive Care Med. 20 (1): 3–17. doi:10.1177/0885066604271539. PMID 15665255.
  32. ↑ Wong ET, Rude RK, Singer FR, Shaw ST (1983). “A high prevalence of [[hypomagnesemia]] and [[hypermagnesemia]] in hospitalized patients”. Am J Clin Pathol. 79 (3): 348–52. doi:10.1093/ajcp/79.3.348. PMID 6829504. URL–wikilink conflict (help)
  33. ↑ Wedenoja S, Höglund P, Holmberg C (2010). “Review article: the clinical management of congenital chloride diarrhoea”. Aliment Pharmacol Ther. 31 (4): 477–85. doi:10.1111/j.1365-2036.2009.04197.x. PMID 19912155.
  34. ↑ EVANSON JM, STANBURY SW (1965). “CONGENITAL CHLORIDORRHOEA OR SO-CALLED CONGENITAL ALKALOSIS WITH DIARRHOEA”. Gut. 6: 29–38. doi:10.1136/gut.6.1.29. PMC 1552247. PMID 14259421.
  35. ↑ “Alkalosis: MedlinePlus Medical Encyclopedia”.
  36. ↑ Gennari FJ (1998). “Hypokalemia”. N Engl J Med. 339 (7): 451–8. doi:10.1056/NEJM199808133390707. PMID 9700180.
  37. ↑ Kim GH, Han JS (2002). “Therapeutic approach to hypokalemia”. Nephron. 92 Suppl 1: 28–32. doi:10.1159/000065374. PMID 12401935.


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Epidemiology and Demographics

Epidemiology and Demographics

Main article: Bartter syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Overview

The prevalence of Barter Syndrome is approximately 1 in 1,000,000 individuals. The annual incidence of the syndrome has been estimated at 1.2 per million people. According to a review of twenty-eight patients with Bartter syndrome during the years 1964-1986 who were followed for an average of 10 years, their mean age at the time of diagnosis was 32.9 years. These patients were observed to have short stature than normal subjects.

Epidemiology and Demographics

Prevalence

  • The prevalence of Barter syndrome is approximately 1 in 1,000,000 individuals.[1]
  • Bartter syndrome is a result of mutations that disable the function of NA-K-Cl channels. This condition leads to prenatal or neonatal death before it can be diagnosed and therefore has a lower prevalence.[1]

Incidence

  • The annual incidence of the syndrome has been estimated at 1.2 per million people.[2]

Age

  • According to a review of twenty-eight patients with Bartter syndrome during the years 1964-1986 who were followed for an average of 10 years, their mean age at the time of diagnosis was 32.9 years. These patients were observed to have short stature than normal subjects.[2]

References

  1. ↑ 1.0 1.1 Ji W, Foo JN, O’Roak BJ, Zhao H, Larson MG, Simon DB; et al. (2008). “Rare independent mutations in renal salt handling genes contribute to blood pressure variation”. Nat Genet. 40 (5): 592–599. doi:10.1038/ng.118. PMC 3766631. PMID 18391953.
  2. ↑ 2.0 2.1 Rudin A (1988). “Bartter’s syndrome. A review of 28 patients followed for 10 years”. Acta Med Scand. 224 (2): 165–71. PMID 3421146.


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Risk Factors

Risk Factors

Main article: Bartter syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Overview

Anyone with a family history of Bartter syndrome is at risk.

Risk Factors

Anyone with a family history of Bartter syndrome is at risk.

References


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Screening

Screening

Main article: Bartter syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Overview

Genetic screening for Bartter syndrome mutated genes can be performed among individuals with unexplained hypertension and hypokalemia.

Screening

References

  1. ↑ Bao M, Cai J, Yang X, Ma W (2019). “Genetic screening for Bartter syndrome and Gitelman syndrome pathogenic genes among individuals with hypertension and hypokalemia”. Clin Exp Hypertens. 41 (4): 381–388. doi:10.1080/10641963.2018.1489547. PMID 29953267.
Natural History, Complications and Prognosis

Natural History, Complications and Prognosis

Main article: Bartter syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Overview

Bartter Syndrome usually occurs in childhood. Bartter syndrome type I and type II are salt-wasting renal tubular disorders that are clinically characterized by polyhydramnios leading to premature delivery, marked polyuria, and a tendency towards nephrocalcinosis. Common complications of Bartter syndrome include Gallstones, Rhabdomyolysis, Prolonged QT interval, Life-threatening arrhythmia, Syncope, Sudden death, weakening of the bones and Renal failure. The limited prognostic information available suggests that early diagnosis and appropriate treatment of infants and young children with classic Bartter Syndrome (type 3) may improve growth and perhaps neuro-intellectual development. On the other hand, sustained hypokalemia and hyperreninemia can cause progressive tubulointerstitial nephritis, resulting in end-stage renal disease (Kidney failure). With the early treatment of the electrolyte imbalances, the prognosis for patients with Classic Bartter Syndrome is good. Patients with Bartter syndrome type I and II tend to present a satisfactory prognosis after a median follow-up of more than 10 years.

Natural History

Complications

Prognosis

  • The prognosis is based on mutations or depends on the degree of the receptor dysfunction.[8]
  • The limited prognostic information available suggests that early diagnosis and appropriate treatment of infants and young children with classic Bartter Syndrome (type 3) may improve growth and perhaps neuro-intellectual development. On the other hand, sustained hypokalemia and hyperreninemia can cause progressive tubulointerstitial nephritis, resulting in end-stage renal disease (Kidney failure). With the early treatment of the electrolyte imbalances, the prognosis for patients with Classic Bartter Syndrome is good.
  • Patients with Bartter syndrome type I and II tend to present a satisfactory prognosis after a median follow-up of more than 10 years.[3]

References

  1. ↑ “Bartter syndrome: MedlinePlus Medical Encyclopedia”.
  2. ↑ Seyberth HW (2008). “An improved terminology and classification of Bartter-like syndromes”. Nat Clin Pract Nephrol. 4 (10): 560–7. doi:10.1038/ncpneph0912. PMID 18695706.
  3. ↑ 3.0 3.1 3.2 Puricelli E, Bettinelli A, Borsa N, Sironi F, Mattiello C, Tammaro F; et al. (2010). “Long-term follow-up of patients with Bartter syndrome type I and II”. Nephrol Dial Transplant. 25 (9): 2976–81. doi:10.1093/ndt/gfq119. PMID 20219833.
  4. ↑ Hacihamdioglu DO, Fidanci K, Kilic A, Gok F, Topaloglu R (2013). “QT and JT dispersion and cardiac performance in children with neonatal Bartter syndrome: a pilot study”. Pediatr Nephrol. 28 (10): 1969–74. doi:10.1007/s00467-013-2517-5. PMID 23760993.
  5. ↑ Scognamiglio R, Negut C, Calò LA (2007). “Aborted sudden cardiac death in two patients with Bartter’s/Gitelman’s syndromes”. Clin Nephrol. 67 (3): 193–7. doi:10.5414/cnp67193. PMID 17390745.
  6. ↑ Reungjui S, Roncal CA, Sato W, Glushakova OY, Croker BP, Suga S; et al. (2008). “Hypokalemic nephropathy is associated with impaired angiogenesis”. J Am Soc Nephrol. 19 (1): 125–34. doi:10.1681/ASN.2007030261. PMC 2391040. PMID 18178802.
  7. ↑ “Bartter syndrome – Genetics Home Reference – NIH”.
  8. ↑ 8.0 8.1 Al Shibli A, Narchi H (2015). “Bartter and Gitelman syndromes: Spectrum of clinical manifestations caused by different mutations”. World J Methodol. 5 (2): 55–61. doi:10.5662/wjm.v5.i2.55. PMC 4482822. PMID 26140272.


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Diagnosis

Diagnosis

History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | X Ray | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies

Treatment

Treatment

Medical Therapy | Surgery | Future or Investigational Therapies | Primary Prevention | Secondary Prevention

Case Studies

Case Studies

Case #1

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