Bartter Syndrome, Type 3

Alternative Names

  • Bartter Syndrome, Classic
  • Bartter Syndrome, Type 3, with Hypocalciuria
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Disorders of other endocrine glands

OMIM Number

607364

Mode of Inheritance

Autosomal recessive

Gene Map Locus

1p36

Description

Bartter syndromes are defined as a family of inherited recessive autosomal heterogeneous renal tubular disorders, or tubulopathies. All disease variants follow autosomal recessive inheritance and share the following characteristic clinical features: renal salt wasting, hypokalemic metabolic alkalosis, normotensive hyperreninemic hyperaldosteronism, and hyperplasia of the juxtaglomerular apparatus.

Bartter syndrome type 3 presents with sequeale of pronounced hypokalemia and marked salt loss resulting in muscle weakness and volume contraction during the first years of life. Nephrocalcinosis is an uncommon finding, and investigation of renal concentrating ability is impaired to a lesser extent than in other variants of Bartter syndrome. Among other features, subnormal response to angiotensin II infusion and a pitressin concentration defect with mental and physical growth delay are common.

Molecular Genetics

Mutations in the gene for the basolateral chloride channel CLCNKB, encoding for a chloride channel in Henle's loop, cause the genetic variant of Bartter syndrome type 3. The CLCNKB channel is a member of the ClC family, which comprises at least 9 mammalian chloride channels, and is believed to have 12 transmembrane domains and intracellular N and C termini.

Seven mutations altering the CLCNKB gene and co-segregating with Bartter syndrome type 3 have been demonstrated. The CLCNKB channel is a member of the CLC family, which comprises at least 9 mammalian chloride channels, and is believed to have 12 transmembrane domains and intracellular N and C termini. It has been demonstrated that barttin acts as an essential beta subunit for the CLCKNB chloride channel, with which it co-localizes in basolateral membranes of renal tubules and of potassium-secreting epithelia of the inner ear. The heteromers formed by the chloride channel and barttin are crucial for renal salt reabsorption and potassium recycling in the inner ear.

 

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
607364.1.1United Arab EmiratesFemaleYesYes Hypokalemic metabolic alkalosisNM_000085.5:c.490G>THomozygousAutosomal, RecessiveAl-Shibli et al. 2014 Patients from this E...
607364.1.2United Arab EmiratesMaleYesYes Hypokalemic metabolic alkalosisNM_000085.5:c.490G>THomozygousAutosomal, RecessiveAl-Shibli et al. 2014 Brother of 607364.1....
607364.1.3United Arab EmiratesFemaleYesYes Hypokalemic metabolic alkalosisNM_000085.5:c.490G>THomozygousAutosomal, RecessiveAl-Shibli et al. 2014 Cousin of 607364.1.1...
607364.1.4United Arab EmiratesFemaleYesYes Hypokalemic metabolic alkalosisNM_000085.5:c.490G>THomozygousAutosomal, RecessiveAl-Shibli et al. 2014 Cousin of 607364.1.1...

Other Reports

Kuwait

Abdel-al (1999) analyzed the prevalence and incidence of Bartter syndrome in Kuwait. Bartter's syndrome was diagnosed in 13 Kuwaiti children over a 14 year period (1981-1995) with the estimated incidence of 1.7/100,000 live births. All patients had hypokalemia, hypochloremia with metabolic alkalosis, hyperreninemia and were normotensive. 

Palestine

Zelikovic et al. (2003) examined the clinical, biochemical and genetic characteristics of a very large inbred Bedouin kindred in the lower Galilee with hereditary hypokalemic tubulopathy. The pattern of inheritance of the disease in the family is compatible with an autosomal recessive trait. Twelve family members affected with hypokalemic tubulopathy, as well as 26 close relatives were clinically and biochemically evaluated. Evaluation of affected family members (age range 3 to 36 years) revealed phenotypic features of both Gitelman syndrome and classic Bartter syndrome. Features typical of classic Bartter syndrome included early age of presentation (<1 year) in 3 (25%), polyuria/dehydration in 4 (33%), growth retardation in 3 (25%), hypercalciuria (urinary calcium/creatinine mmol/mmoverline>0.55) in 4 (33%) and nephrolithiasis in 1 (8%).

Saudi Arabia

Malik et al. (1997) evaluated the parents and siblings of a Bartter syndrome patient for renal tubular function. The father and all 9 siblings of the patient had biochemical features of Bartter syndrome. His mother, a first cousin of his father, had hypokalemia and hyperkaluria but no other features of Bartter syndrome and could have been a 'carrier'. The mother and all 9 siblings were asymptomatic. Including the patient, hypomagnesemia was present in 8 of 12 family members. Therapy with a combination of potassium chloride and magnesium increased the serum potassium and magnesium levels to within normal limits. Malik et al. (1997) indicated that the presence of one affected parent and involvement of all siblings of the patient raise the possibility of an autosomal dominant inheritance in their family.

Syria

El-Kishawi et al. (2005) reported a pair of dizygotic twins suffering from neonatal Bartter syndrome with abnormal onset of early hyperkalemia who presented at Farwaniya Hospital in Kuwait. Both subjects, a boy and a girl, were born at 25 weeks gestation to consanguineous first degree cousins from Syria with five healthy children. The subjects had a birth weight of 900g and 600g, respectively. The boy passed away at an age of 5 days after experiencing severe hyperkalemia and the girl lived but suffered from developmental retardation and failure to thrive. El-Kishawi et al. (2005) suggested that these two cases were the first to be reported from Kuwait.

[El-Kishawi A, Soni A, Al-Saleh Q. Neonatal Bartter syndrome with early hyperkalemia: an unusual presentation in twins. Kuwait Medical Journal 2005, 37 (2): 130-2.]

United Arab Emirates

Abou-Chaaban et al. (1997) studied the pattern of pediatric renal diseases among children in the Dubai Emirate during the period from 1991 to 1996. In this period, a total of 712 pediatric patients, including 230 nationals of the United Arab Emirates, were seen with various renal problems. In their study, Abou-Chaaban et al. (1997) observed two cases of Bartter's syndrome among nationals of the United Arab Emirates.

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