Bartter syndrome
Encyclopedia
Bartter syndrome is a rare inherited defect in the thick ascending limb of the loop of Henle
. It is characterized by low potassium levels (hypokalemia
) , increased blood pH (alkalosis
), and normal to low blood pressure. There are two types of Bartter syndrome: neonatal and classic. A closely associated disorder, Gitelman syndrome
, is milder than both subtypes of Bartter syndrome.
(polyhydramnios). After birth, the infant is seen to urinate and drink excessively (polyuria
, and polydipsia
, respectively). Life-threatening dehydration may result if the infant does not receive adequate fluids. About 85% of infants dispose of excess amounts of calcium in the urine (hypercalciuria
) and kidneys (nephrocalcinosis
), which may lead to kidney stone
s. In rare occasions, the infant may progress to renal failure.
Patients with classic Bartter syndrome may have symptoms in the first two years of life, but they are usually diagnosed at school age or later. Like infants with the neonatal subtype, patients with classic Bartter syndrome also have polyuria, polydipsia, and a tendency to dehydration, but normal or just
slightly increased urinary calcium excretion without the tendency to develop kidney stones. These patients also have vomiting and growth retardation. Kidney function is also normal if the disease is treated, but occasionally patients proceed to end-stage renal failure.
Bartter's syndrome consists of hypokalaemia, alkalosis, normal to low blood pressures, and elevated plasma renin and aldosterone. Numerous causes of this syndrome probably exist. Diagnostic pointers include high urinary potassium and chloride despite low serum values, increased plasma renin, hyperplasia
of the juxtaglomerular apparatus
on renal biopsy
, and careful exclusion of diuretic abuse. Excess production of renal prostaglandins is often found. Magnesium wasting may also occur.
.
The clinical findings characteristic of Bartter syndrome are hypokalemia, metabolic alkalosis, and normal to low blood pressure. These findings may also be caused by:
Patients with Bartter syndrome may also have elevated renin
and aldosterone
levels.
Prenatal Bartter syndrome can be associated with polyhydramnios
.
of the nephron.
Bartter and Gitelman syndromes can be divided into different subtypes based on the genes involved:
is also used to reduce potassium loss.
Nonsteroidal antiinflammatory drugs (NSAIDs) can be used as well, and are particularly helpful in patients with neonatal Bartter's syndrome.
Angiotensin-converting enzyme (ACE) inhibitors
can also be used.
, who, along with Dr. Pacita Pronove, first described it in 1960 and in more patients in 1962.
Pseudo-Bartter’s syndrome is a syndrome of similar presentation as Bartter syndrome but without any of its characteristic genetic defects. Pseudo-Bartter’s syndrome has been seen in cystic fibrosis
, as well as in excessive use of laxative
s.
Loop of Henle
In the kidney, the loop of Henle is the portion of a nephron that leads from the proximal convoluted tubule to the distal convoluted tubule. Named after its discoverer F. G. J...
. It is characterized by low potassium levels (hypokalemia
Hypokalemia
Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
) , increased blood pH (alkalosis
Alkalosis
Alkalosis refers to a condition reducing hydrogen ion concentration of arterial blood plasma . Generally, alkalosis is said to occur when pH of the blood exceeds 7.45. The opposite condition is acidosis .-Causes:...
), and normal to low blood pressure. There are two types of Bartter syndrome: neonatal and classic. A closely associated disorder, Gitelman syndrome
Gitelman syndrome
Gitelman syndrome is a rare inherited defect in the distal convoluted tubule of the kidneys. It causes the kidneys to pass sodium, magnesium, chloride, and potassium into the urine, rather than allowing it to be resorbed into the bloodstream....
, is milder than both subtypes of Bartter syndrome.
Features
In 90% of cases, neonatal Bartter syndrome is seen between 24 and 30 weeks of gestation with excess amniotic fluidAmniotic sac
The amniotic sac is the sac in which the fetus develops in amniotes. It is a tough but thin transparent pair of membranes, which hold a developing embryo until shortly before birth. The inner membrane, the amnion, contains the amniotic fluid and the fetus. The outer membrane, the Chorion,...
(polyhydramnios). After birth, the infant is seen to urinate and drink excessively (polyuria
Polyuria
Polyuria is a condition usually defined as excessive or abnormally large production or passage of urine . Frequent urination is sometimes included by definition, but is nonetheless usually an accompanying symptom...
, and polydipsia
Polydipsia
Polydipsia is a medical symptom in which the patient displays excessive thirst. The word derives from the Greek πολυδιψία, which is derived from πολύς + δίψα...
, respectively). Life-threatening dehydration may result if the infant does not receive adequate fluids. About 85% of infants dispose of excess amounts of calcium in the urine (hypercalciuria
Hypercalciuria
Hypercalciuria or hypercalcinuria is the condition of elevated calcium in the urine. Chronic hypercalcinuria may lead to impairment of renal function, nephrocalcinosis, and renal insufficiency....
) and kidneys (nephrocalcinosis
Nephrocalcinosis
Nephrocalcinosis, once known as Albright's calcinosis after Fuller Albright, is a term originally used to describe deposition of calcium salts in the renal parenchyma due to hyperparathyroidism. It is now more commonly used to describe diffuse, fine, renal parenchymal calcification on radiology...
), which may lead to kidney stone
Kidney stone
A kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...
s. In rare occasions, the infant may progress to renal failure.
Patients with classic Bartter syndrome may have symptoms in the first two years of life, but they are usually diagnosed at school age or later. Like infants with the neonatal subtype, patients with classic Bartter syndrome also have polyuria, polydipsia, and a tendency to dehydration, but normal or just
slightly increased urinary calcium excretion without the tendency to develop kidney stones. These patients also have vomiting and growth retardation. Kidney function is also normal if the disease is treated, but occasionally patients proceed to end-stage renal failure.
Bartter's syndrome consists of hypokalaemia, alkalosis, normal to low blood pressures, and elevated plasma renin and aldosterone. Numerous causes of this syndrome probably exist. Diagnostic pointers include high urinary potassium and chloride despite low serum values, increased plasma renin, hyperplasia
Hyperplasia
Hyperplasia means increase in number of cells/proliferation of cells. It may result in the gross enlargement of an organ and the term is sometimes mixed with benign neoplasia/ benign tumor....
of the juxtaglomerular apparatus
Juxtaglomerular apparatus
The juxtaglomerular apparatus is a microscopic structure in the kidney, which regulates the function of each nephron. The juxtaglomerular apparatus is named for its proximity to the glomerulus: it is found between the vascular pole of the renal corpuscle and the returning distal convoluted tubule...
on renal biopsy
Renal biopsy
A renal biopsy is a procedure in which a sample of kidney tissue is obtained. Microscopic examination of the tissue can provide information needed to diagnose, monitor or treat a renal disorder.-Indications:...
, and careful exclusion of diuretic abuse. Excess production of renal prostaglandins is often found. Magnesium wasting may also occur.
Diagnosis
People suffering from Bartter syndrome present symptoms that are identical to those of patients who are on loop diuretics like furosemideFurosemide
Furosemide or frusemide is a loop diuretic used in the treatment of congestive heart failure and edema. It is most commonly marketed by Sanofi-Aventis under the brand name Lasix...
.
The clinical findings characteristic of Bartter syndrome are hypokalemia, metabolic alkalosis, and normal to low blood pressure. These findings may also be caused by:
- Chronic vomiting: These patients will have low urine chloride levels (Bartter's will have relatively higher urine chloride levels).
- Abuse of diureticDiureticA diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
medications (water pills): The physician must screen urine for multiple diuretics before diagnosis is made. - Magnesium deficiencyMagnesium deficiency (medicine)Magnesium deficiency refers to an intake of dietary magnesium below minimal levels, which can result in numerous symptoms and diseases. These can generally be remedied by an increase of magnesium in diet or oral supplements...
and Calcium deficiency: These patients will also have low serum and urine magnesium and calcium
Patients with Bartter syndrome may also have elevated renin
Renin
Renin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...
and aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
levels.
Prenatal Bartter syndrome can be associated with polyhydramnios
Polyhydramnios
Polyhydramnios is a medical condition describing an excess of amniotic fluid in the amniotic sac. It is seen in 0.2 to 1.6% of pregnancies,,...
.
Pathophysiology
Bartter syndrome is caused by mutations of genes encoding proteins that transport ions across renal cells in the thick ascending limbThick ascending limb of loop of Henle
The thick ascending limb of loop of Henle also known as distal straight tubule, is a segment of the nephron in the kidney. It can be divided into two parts: that in the renal medulla, and that in the renal cortex.-Medullary thick ascending limb:...
of the nephron.
Bartter and Gitelman syndromes can be divided into different subtypes based on the genes involved:
| Name | Bartter type | Associated gene mutations | Defect >- | neonatal Bartter's syndrome |
type 1 | NKCC2 Na-K-2Cl symporter The Na-K-Cl cotransporter is a protein that aids in the active transport of sodium, potassium, and chloride into and out of cells. There are two varieties, or isoforms, of this membrane transport protein, called NKCC1 and NKCC2. NKCC1 is widely distributed throughout the body; it has important... |
Na-K-2Cl symporter Na-K-2Cl symporter The Na-K-Cl cotransporter is a protein that aids in the active transport of sodium, potassium, and chloride into and out of cells. There are two varieties, or isoforms, of this membrane transport protein, called NKCC1 and NKCC2. NKCC1 is widely distributed throughout the body; it has important... >- | neonatal Bartter's syndrome |
type 2 | ROMK ROMK ROMK is an acronym for the Renal Outer Medullary Potassium channel. This is an ATP-dependent potassium channel that transports potassium out of cells. It plays an important role in potassium recycling in the thick ascending limb and potassium secretion in the cortical collecting duct of the... |
+ channel >- | classic Bartter's syndrome |
type 3 | CLCNKB CLCNKB Chloride channel Kb, also known as CLCNKB, is a protein which in humans is encoded by the CLCNKB gene.Chloride channel Kb is a member of the CLC family of voltage-gated chloride channels, which comprises at least 9 mammalian chloride channels. Each is believed to have 12 transmembrane domains and... |
- channel >- | Bartter's syndrome with sensorineural deafness |
type 4 | BSND BSND Bartter syndrome, infantile, with sensorineural deafness , also known as BSND, is a human gene which is associated with Bartter syndrome.-Further reading:... |
- channel accessory subunit >- | Bartter's syndrome associated with autosomal dominant hypocalcemia |
type 5 | CASR Calcium-sensing receptor The calcium-sensing receptor is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone .-Signal transduction:The release of PTH is... |
calcium-sensing receptor Calcium-sensing receptor The calcium-sensing receptor is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone .-Signal transduction:The release of PTH is... >- | Gitelman's syndrome |
- | SLC12A3 (NCCT) | Sodium-chloride symporter Sodium-chloride symporter The sodium-chloride symporter is a cotransporter in the kidney which has the function of reabsorbing sodium and chloride ions from the tubular fluid into the cells of the distal convoluted tubule of the nephron.It is a member of the SLC12... |
Treatment
While patients should be encouraged to include liberal amounts of sodium and potassium in their diet, potassium supplements are usually required, and spironolactoneSpironolactone
Spironolactone , commonly referred to as simply spiro, is a diuretic and is used as an antiandrogen.It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of pharmaceuticals called...
is also used to reduce potassium loss.
Nonsteroidal antiinflammatory drugs (NSAIDs) can be used as well, and are particularly helpful in patients with neonatal Bartter's syndrome.
Angiotensin-converting enzyme (ACE) inhibitors
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
can also be used.
Prognosis
The limited prognostic information available suggests that early diagnosis and appropriate treatment of infants and young children with Classic Bartter Syndrome may improve growth and perhaps neurointellectual development. On the other hand, sustained hypokalemia and hyperreninemia can cause progressive tubulointerstitial nephritis, resulting in end-stage-renal disease (Kidney failure). With early treatment of the electrolyte imbalances the prognosis for patients with Classic Bartter Syndrome is good.History
The condition is named after Dr. Frederic BartterFrederic Bartter
Frederic Crosby Bartter was an American endocrinologist best known for his work on hormones affecting the kidney and his discovery of syndrome of inappropriate antidiuretic hormone and Bartter syndrome...
, who, along with Dr. Pacita Pronove, first described it in 1960 and in more patients in 1962.
Related conditions
- Bartter and Gitelman syndromeGitelman syndromeGitelman syndrome is a rare inherited defect in the distal convoluted tubule of the kidneys. It causes the kidneys to pass sodium, magnesium, chloride, and potassium into the urine, rather than allowing it to be resorbed into the bloodstream....
s are both characterized by hypokalemia, normal to low blood pressure, and hypochloremic metabolic alkalosis.
Pseudo-Bartter’s syndrome is a syndrome of similar presentation as Bartter syndrome but without any of its characteristic genetic defects. Pseudo-Bartter’s syndrome has been seen in cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
, as well as in excessive use of laxative
Laxative
Laxatives are foods, compounds, or drugs taken to induce bowel movements or to loosen the stool, most often taken to treat constipation. Certain stimulant, lubricant, and saline laxatives are used to evacuate the colon for rectal and/or bowel examinations, and may be supplemented by enemas under...
s.