comprehensive ppt on bartter syndrome

1. Dr.Afnan Shamraiz
PGr.Paeds
ATH

2. Background

Bartter syndrome, originally described by
Bartter and colleagues in 1962, represents
a set of closely related, autosomal
recessive renal tubular disorders
characterized by hypokalemia,
hypochloremia, metabolic alkalosis, and
hyperreninemia with normal blood
pressure. The underlying renal abnormality
results in excessive urinary losses of
sodium, chloride, and potassium.

3. Pathophysiology


Bartter and Gitelman syndromes are renal
tubular salt-wasting disorders in which the
kidneys cannot reabsorb chloride in the TALH
or the DCT, depending on the mutation.
Chloride is passively absorbed along most of
the proximal tubule but is actively transported
in the TALH and the distal convoluted tubule
(DCT). Failure to reabsorb chloride results in a
failure to reabsorb sodium and leads to
excessive sodium and chloride (salt) delivery
to the distal tubules, leading to excessive salt
and water loss from the body.

4. Other pathophysiologic abnormalities result from
excessive salt and water loss. The renin-angiotensinaldosterone system (RAAS) is a feedback system
activated with volume depletion. Long-term stimulation
may lead to hyperplasia of the juxtaglomerular complex.
 Angiotensin II (ANG II) is directly
vasoconstrictive, increasing systemic and renal
arteriolar constriction, which helps to prevent systemic
hypotension. It directly increases proximal tubular
sodium reabsorption.
 ANG II–induced renal vasoconstriction, along with
potassium deficiency, produces a counterregulatory rise
in vasodilating prostaglandin E (PGE) levels. High PGE
levels are associated with growth inhibition in children.


5. 
High levels of aldosterone also enhance
potassium and hydrogen exchange for
sodium. Excessive intracellular hydrogen ion
accumulation is associated with hypokalemia
and intracellular renal tubule potassium
depletion. This is because hydrogen is
exchanged for potassium to maintain electrical
neutrality. It may lead to intracellular citrate
depletion, because the alkali salt is used to
buffer the intracellular acid and then lowers
urinary citrate excretion. Hypocitraturia is an
independent risk factor for renal stone
formation.

6. 
Excessive distal sodium delivery increases
distal tubular sodium reabsorption and
exchange with the electrically equivalent
potassium or hydrogen ion. This, in
turn, promotes hypokalemia, while lack of
chloride reabsorption promotes inadequate
exchange of bicarbonate for chloride, and
the combined hypokalemia and excessive
bicarbonate retention lead to metabolic
alkalosis

7. 

Persons with Bartter syndrome often have hypercalciuria.
Normally, reabsorption of the negative chloride ions
promotes a lumen-positive voltage, driving paracellular
positive calcium and magnesium absorption. Continued
reabsorption and secretion of the positive potassium ions
into the lumen of the TALH also promotes reabsorption of
the positive calcium ions through paracellular tight junctions.
Dysfunction of the TALH chloride transporters prevents urine
calcium reabsorption in the TALH. Excessive urine calcium
excretion may be one factor in the nephrocalcinosis
observed in these patients.
Calcium is usually reabsorbed in the DCT. Theoretically,
chloride is reabsorbed through the thiazide-sensitive sodium
chloride cotransporter and transported from the cell through
a basolateral chloride channel, reducing intracellular chloride
concentration. The net effect is increased activity of the
voltage-dependent calcium channels and enhanced
electrical gradient for calcium reabsorption from the lumen.

8. In Gitelman syndrome, dysfunction of
the sodium chloride cotransporter
(NCCT) leads to hypocalciuria and
hypomagnesemia. In the last several
years, the understanding of magnesium
handling by the kidney has improved
and advances in genetics have allowed
the differentiation of a variety of
magnesium-handling mutations.
 While patients the variants that make
up Bartter syndrome may or may not
havehypomagnesemia, this condition is
pathognomonic for Gitelman syndrome.
The mechanism of the impaired
magnesium reabsorption is still
unknown; studies in NCCT knockout
mice demonstrate increased apoptosis
of DCT cells, which would then lead to
diminished reabsorptive surface area.


9. 

The ClC-Kb channel is found in the basolateral membrane of
the TALH, while the barttin subunits of ClC-Ka and ClC-Kb are
found in the basolateral membrane of the marginal cells of the
cochlear stria vascularis.
In the inner ear, an Na-K-2Cl pump, called NKCC1, on the
basolateral membrane increases intracellular levels of sodium,
potassium, and chloride. Potassium excretion across the
apical membrane against a concentration gradient produces
the driving force for the depolarizing influx of potassium
through the ion channels of the sensory hair cells required for
hearing. The sodium ion is excreted across the basolateral
membrane by the Na-K-adenosine triphosphatase (ATPase)
pump, and the ClC-K channels allow the chloride ion to exit to
maintain electroneutrality.

10. Sensorineural deafness
associated with type IV
Bartter syndrome, a
neonatal form of the
disease (see Etiology),
is due to defects in the
barttin subunit of the
ClC-Ka and CIC-Kb
channels.
 Mutations in only the
ClC-Kb subunit, as
occurs in type III Bartter
syndrome, do not result
in sensorineural deafnes


11. Etiology
Defects in either the sodium chloride/potassium
chloride cotransporter or the potassium channel
affect the transport of sodium, potassium, and
chloride in the thick ascending limb of the loop of
Henle (TALH). The result is the delivery of large
volumes of urine with a high content of these
ions to the distal segments of the renal
tubule, where only some sodium is reabsorbed
and potassium is secreted.
 Familial and sporadic forms of Bartter and
Gitelman syndromes exist. When
inherited, these syndromes are passed on as
autosomal recessive conditions.


12. Normal transport mechanism

Normal transport mechanisms in
the thick ascending limb of the
loop of Henle. Reabsorption of
sodium chloride is achieved with
the sodium chloride/potassium
chloride cotransporter, which is
driven by the low intracellular
concentrations of
sodium, chloride, and
potassium. Low concentrations
are maintained by the
basolateral sodium pump
(sodium-potassium adenosine
triphosphatase), the basolateral
chloride channel (ClC-kb), and
the apical potassium channel
(ROMK).

13. NORMAL

15. Neonatal (type I and type II)
Bartter syndrome


An autosomal recessive mode of inheritance is
observed in some patients with neonatal
Bartter syndrome, although many cases are
sporadic.
At least 2 genotypes have been identified in
neonatal Bartter syndrome. Type I results from
mutations in the sodium chloride/potassium
chloride cotransporter gene (NKCC2; locus
SLC12A1 on chromosome bands 15q15-21).
Type II results from mutations in
the ROMK gene (locus KCNJ1 on
chromosome bands 11q24-25).

16. 
Type I neonatal
Bartter
syndrome.
Mutations in
the sodium
chloride/potassi
um chloride
cotransporter
gene result in
defective
reabsorption of
sodium, chlorid
e, and
potassium.

17. 
Type II neonatal
Bartter
syndrome.
Mutations in the
ROMK gene
result in an
inability to
recycle
potassium from
the cell back
into the tubular
lumen, with
resultant
inhibition of the
sodium
chloride/potassi
um chloride
cotransporter.

18. Classic (type III) Bartter
syndrome
Some patients have an autosomal
recessive mode of inheritance in classic
Bartter syndrome, although many cases
are sporadic.
 In classic Bartter syndrome, the defect in
sodium reabsorption appears to result from
mutations in the chloride-channel gene (on
band 1p36). The consequent inability of
chloride to exit the cell inhibits the sodium
chloride/potassium chloride cotransporter.


19. 
Classic Bartter
syndrome.
Mutations in the
ClC-kb chloride
channel lead to
an inability of
chloride to exit
the cell, with
resultant
inhibition of the
sodium
chloride/potassi
um chloride
cotransporter.

20. 
Increased delivery of sodium

chloride to the distal sites of
the nephron leads to salt
wasting, polyuria, volume
contraction, and stimulation
of the renin-angiotensinaldosterone axis. These
effects, combined with
biologic adaptations of
downstream tubular
segments, specifically the
distal convoluted tubule
(DCT) and the collecting
duct, result in hypokalemic
metabolic alkalosis.[2]
The hypokalemia, volume
contraction, and elevated
angiotensin levels increase
intrarenal prostaglandin E2
(PGE2) synthesis, which
contributes to a vicious
cycle by further stimulating
the renin-aldosterone axis
and inhibiting sodium
chloride reabsorption in the
TALH.

21. Type IV Bartter syndrome

Studies have identified a novel
type IV Bartter syndrome.[10, 23,
24] This is a type of neonatal
Bartter syndrome associated
with sensorineural deafness
and has been shown to be
caused by mutations in
the BSND gene.[23, 25,
26] BSND encodes barttin, an
essential beta subunit that is
required for the trafficking of
the chloride channel ClC-K
(ClC-Ka and ClC-Kb) to the
plasma membrane in the TALH
and the marginal cells in the
scala media of the inner ear
that secrete potassium ion ̶
rich endolymph.[10] Thus, lossof-function mutations in barttin
cause Bartter syndrome with
sensorineural deafness.

22. 
In contrast to other Bartter types, the
underlying genetic defect in type IV is
not directly in an ion-transporting
protein. The defect instead indirectly
interferes with the barttin-dependent
insertion in the plasma membrane of
chloride channel subunits ClC-Ka and
ClC-Kb.

23. Type V Bartter syndrome

Other observations have identified type V
Bartter syndrome. This is another type of
neonatal Bartter syndrome that is associated
with sensorineural deafness, but it is not
caused by mutations in the BSND gene. Type
V Bartter syndrome has been shown to be a
digenic disorder resulting from loss-of-function
mutations in the genes that encode the
chloride channel subunits ClC-Ka and ClCKb.[27] The specific genetic defect includes a
large deletion in the gene that encodes ClC-Kb
(ie, CLCNKB) and a point mutation in the gene
that encodes ClC-Ka (CLCNKA).

24. Summary of Pathophysiology
Hypokalemic salt-losing tubulopathies_Zelikovic_Nephrology Dialysis Transplant_2003

25. A summary of currently identified genotype-phenotype
correlations in Bartter syndrome is in the table below. For
completion, the genetic defect found in Gitelman syndrome
(the thiazide-sensitive sodium chloride cotransporter,
encoded by the gene NCCT) is also included.
Bartter Syndrome Genotype-Phenotype Correlations
Genetic Type
Defective Gene
Clinical Type
Bartter type I
NKCC2
Neonatal
Bartter type II
ROMK
Neonatal
Bartter type III
CLCNKB
Classic
Bartter type IV
BSND
Neonatal with deafness
Bartter type V
CLCNKB and CLCNKA
Neonatal with deafness
Gitelman syndrome
NCCT
Gitelman syndrome

26. Cascade of events
Salt loss
Volume depletion
Renin/aldosterone secretion / JGA hyperplasia
autonomous hyperreninemic hyperaldosteronism
Enhanced K and H secertion at the collecting tubule
Hypokalemia and metabolic alkalosis result

27. Epidemiology
International occurrence
Bartter syndrome is rare, and estimates of its occurrence vary
from country to country. In the United States, the precise
incidence is unknown.
 In Costa Rica, the frequency of neonatal Bartter syndrome is
approximately 1.2 cases per 100,000 live births but is higher if
all preterm births are considered. No evidence of consanguinity
was found in the Costa Rican cohort.
 In Kuwait, the prevalence of consanguineous marriages or
related families in patients with Bartter syndrome is higher than
50%, and prevalence in the general population is 1.7 cases per
100,000 persons.
 In Sweden, the frequency has been calculated as 1.2 cases per
1 million persons. Of the 28 patients Rudin reported, 7 came
from 3 families; the others were unrelated.[14]



28. Age-related demographics

Neonatal Bartter syndrome can be
suspected before birth or can be
diagnosed immediately after birth. In the
classic form, symptoms begin in
neonates or in infants aged 2 years or
younger. Gitelman syndrome is often not
diagnosed until adolescence or early
adulthood.[15, 16]

29. PRESENTATION

30. History




Neonatal Bartter syndrome
Maternal polyhydramnios, secondary to fetal
polyuria, is evident by 24-30 weeks' gestation.
Delivery often occurs before term. The newborn has
massive polyuria (rate as high as 12-50 mL/kg/h).
The subsequent course is characterized by lifethreatening episodes of fluid loss, clinical volume
depletion, and failure to thrive. Volume depletion
increases thirst, and the normal response is to
increase fluid intake.
A subset of patients with neonatal Bartter syndrome
(types IV and V) develop sensorineural deafness.

31. Classic Bartter syndrome









Patients have a history of maternal
polyhydramnios and premature delivery.
Symptoms include the following:
Polyuria
Polydipsia
Vomiting
Constipation
Salt craving
Tendency for volume depletion
Failure to thrive
Linear growth retardation

32. Other symptoms
Other symptoms, which appear during
late childhood, include fatigue, muscle
weakness, cramps, and recurrent
carpopedal spasms.
 Developmental delay and minimal brain
dysfunction with nonspecific
electroencephalographic changes are
also present.


33. Physical Examination
Neonatal Bartter syndrome
Patients are thin and have reduced muscle
mass and a triangularly shaped face, which
is characterized by a prominent forehead,
large eyes, protruding ears, and drooping
mouth. Strabismus is frequently present.
Blood pressure is within the reference
range.
 A subset of patients with Bartter syndrome
(types IV and V) develop sensorineural
deafness, which is detectable with
audiometry.



34. Classic Bartter syndrome



The patient's facial appearance may be similar to
that encountered in the neonatal type. However, this
finding is infrequent.
Patients with Gitelman syndrome tend to have milder
symptoms than do those with Bartter syndrome and
to present in adolescence and early adulthood.
Often, patients have minimal symptomatology and
lead relatively normal lives.[14]
Consider possible renal tubular disorder if
patients, especially dehydrated infants and young
children, are found to have hypokalemia and a high
serum bicarbonate concentration that do not correct
with potassium and chloride replacement treatment.

35. Clinical and biochemical features of Gitelman's
syndrome and the various types of Bartter's
syndrome

36. Differential Diagnosis















Conditions to consider in the differential diagnosis of Bartter
syndrome include the following:
Diuretic abuse
Gitelman syndrome
Hyperprostaglandin E syndrome
Familial hypomagnesemia with hypercalciuria/nephrocalcinosis
Activating mutations of the CaSR calcium-sensing receptor
Cyclical vomiting
Congenital chloride diarrhea
Gullner syndrome - Familial hypokalemic alkalosis with proximal
tubulopathy
Mineralocorticoid excess
Pyloric stenosis
Hypomagnesemia
Cystic fibrosis
Hypochloremic alkalosis
Hypokalemia

37. Morbidity and mortality
Significant morbidity and mortality occur if
Bartter syndrome is untreated. With
treatment, the outlook is markedly
improved; however, long-term prognosis
remains guarded because of the slow
progression to chronic renal failure due to
interstitial fibrosis.
 Sensorineural deafness
 Sensorineural deafness associated with
Bartter syndrome IV is due to defects in the
barttin subunit of the ClC-Ka and CIC-Kb
channels.


38. 





Nephrocalcinosis
A review of 61 cases of Bartter syndrome reported 29 with
nephrocalcinosis, a condition that is often associated with
hypercalciuria.
Renal failure
Renal failure is fairly uncommon in Bartter syndrome. In a
review of 63 patients, 5 developed progressive renal
disease requiring dialysis or transplantation.
In 2 reports of patients who underwent biopsies before
developing end-stage renal disease (ESRD), 1 patient
had interstitial nephritis, and the other had mesangial and
interstitial fibrosis.
One report relates the case of a patient developing
reversible acute renal failure from rhabdomyolysis due to
hypokalemia.

39. Short stature/growth retardation
 Nearly all patients with Bartter syndrome
have growth retardation. In a review of
66 patients, 62 had growth
retardation, often severe (below the fifth
percentile for age). Treatment with
potassium, indomethacin, and growth
hormone (GH) has been effective.


40. 




Additional complications
Other complications in Bartter syndrome
include the following:
Cardiac arrhythmia and sudden death May result from electrolyte imbalances
Failure to thrive and developmental delay Common in untreated patients
Significant decrease in bone mineral
density - Has been documented in patients
with either the neonatal or classic form

41. Workup



Approach Considerations
The severity and site of the mutation determines the age at
which symptoms first develop. Completely dysfunctional
mutations in the receptors and ion channels in the thick
ascending limb of the loop of Henle (TALH) are probably not
compatible with life.
Most cases of Bartter syndrome are discovered in infancy or
early adolescence. Bartter syndrome can also be diagnosed
prenatally, when the fetus develops polyhydramnios and
intrauterine growth retardation. Many of the neonates are
born prematurely. Children diagnosed early in life usually
have more severe electrolyte disorders and symptoms.
Because of Bartter syndrome's heterogeneity, patients with
minimal symptomatology may be discovered relatively late.

42. 





Electrocardiography
An electrocardiogram (ECG) may reveal changes
characteristic of hypokalemia, such as flattened T waves and
prominent U waves.
Histologic findings
Although renal biopsy is not usually required, histologic
findings may be useful in confirming the diagnosis of Bartter
syndrome.
In neonatal and classic Bartter syndrome, the cardinal finding
is hyperplasia of the juxtaglomerular apparatus. Less
frequently, hyperplasia of the medullary interstitial cells is
present.
Glomerular hyalinization, apical vacuolization of the proximal
tubular cells, tubular atrophy, and interstitial fibrosis may be
present as a consequence of chronic hypokalemia.

43. Laboratory Studies





Potassium
Initiate timed urine collection to determine potassium levels. In hypokalemia, normal
kidneys retain potassium.[18] Elevated urinary potassium levels with low blood
potassium levels suggest that the kidneys are having problems retaining potassium.
Aldosterone
Next, initiate timed urine collection to determine aldosterone levels. Aldosterone levels
should be high in volume-replete patients. If urinary aldosterone levels are high
despite volume replacement, there is an abnormal stimulation of aldosterone.
Patients with primary hyperaldosteronism in a volume-replete state usually have
normal to high blood pressure. Low or low-normal blood pressure with high
aldosterone excretion suggests that the primary problem is something else and that
the aldosterone response is secondary to the undiagnosed primary abnormality.

44. 





Chloride
Next, initiate a timed urine collection to determine chloride levels.
Extrarenal volume depletion is a possible reason for low blood
pressure, high aldosterone excretion, and potassium loss. In this
case, the kidneys retain sodium and chloride, and urinary chloride
concentrations should be low.
High urine chloride levels with low blood pressure, high aldosterone
secretion, and high urinary potassium levels are found only with
long-term diuretic use and Bartter or Gitelman syndrome. If diuretic
abuse is suspected, a urine screen for diuretics can be ordered.
Otherwise, the diagnosis is Bartter or Gitelman syndrome.
Calcium/magnesium
Patients with Bartter syndrome have high urinary excretion of
calcium and normal urinary excretion of magnesium.
In patients with Gitelman syndrome, the opposite is true, with tests
showing low urinary excretion of calcium and high urinary excretion
of magnesium.

45. 








Hyperuricemia
Hyperuricemia is present in 50% of patients with Bartter syndrome,
whereas in Gullner syndrome, hypouricemia, secondary to impaired
proximal tubular function, is present.
Complete blood count
Polycythemia may be present from hemoconcentration.
Mutations
Mutations in the different transporters cause Bartter syndrome. The
older methods of determining the presence of mutations require
more detailed physiologic investigations, including determination of
serum magnesium levels and further urine collections to assess
calcium, magnesium, and PGE2 levels.
In Bartter syndrome, urine calcium excretion is high, leading to
nephrocalcinosis, while serum magnesium levels are normal.
With the transporter mutations that cause Gitelman syndrome,
hypomagnesemia is common and is accompanied by hypocalciuria.
Genetic analysis has become the preferred methodology for
determining if a mutation in one of the transporters has occurred. An
analysis of the genes for the transporters shows multiple problems
leading to abnormal gene function, including missense, frame-shift,
loss-of-function, and large deletion mutations. (Not all mutations
lead to a marked loss of function.)[3, 4, 5, 6, 19, 20]

46. 



Amniotic fluid
If the diagnosis is being made
prenatally, assess the amniotic fluid. The
chloride content may be elevated in either
Gitelman or Bartter syndrome.
Glomerular filtration rate
The glomerular filtration rate (GFR) is
preserved during the early stages of the
disease; however, it may decrease as a result
of chronic hypokalemia. One
study, however, hypothesizes that GFR is
affected more by secondary
hyperaldosteronism than by hypokalemia.[29]

47. Imaging Studies



Neonatal Bartter syndrome can be diagnosed best
prenatally by ultrasonography. The fetus may have
polyhydramnios and intrauterine growth retardation.
Amniotic chloride levels may be elevated.[21]
After birth, especially if the disease is diagnosed in
older patients who have hypercalciuria, consider a
renal ultrasonogram or flat plate of the abdomen for
nephrocalcinosis. Sonographic findings include
diffusely increased echogenicity, hyperechoic
pyramids, and interstitial calcium deposition.
Because continued calcium loss may affect
bones, dual-energy radiographic absorptiometry
scans to determine bone mineral density may be
advisable in older patients.

48. 
Nephrocalcinosis can occur and is often
associated with hypercalciuria. It can be
diagnosed with abdominal radiographs,
intravenous pyelograms (IVPs), renal
ultrasonograms, or spiral computed
tomography (CT) scans.

49. Treatment

50. Approach Considerations







Since first described in 1962, several types of medical
treatment have been used, including the following:
Sodium and potassium supplements - Used for the
electrolyte imbalances
Aldosterone antagonists and diuretic spironolactone - Are
mainstays of therapy
Angiotensin-converting enzyme (ACE) inhibitors - Used to
counteract the effects of angiotensin II (ANG II) and
aldosterone
Indomethacin - Used to decrease prostaglandin excretion
Growth hormone (GH) - Used to treat short stature
Calcium or magnesium supplements - May occasionally be
needed if tetany or muscle spasms are present

51. Pregnancy-related
considerations


Reports associated with Bartter syndrome in
pregnant women are limited because Bartter
syndrome is a rare disease. Complications related
to electrolyte loss (eg, hypokalemia,
hypomagnesemia) responded well to
supplementation. Fetuses were unaffected and
carried to term.
In Rudin's report of 28 pregnant patients, no
problems were noted except asymptomatic
hypokalemia.[14] In another study, of 40 patients, 30
reported normal pregnancies and terminated by
normal parturition; however, many of the patients
who were pregnant probably had Gitelman
syndrome

52. 





Inpatient care
For patients initially diagnosed in the hospital, the goal is to
stabilize the patient sufficiently for discharge. This includes
stabilization of potassium and other electrolytes, as well as volume
and, perhaps, acid-base parameters.
Consultations
Contact a nephrologist or pediatric nephrologist whenever a
patient fitting the clinical picture of Bartter or Gitelman syndrome is
identified. The specialist can assist with the initial diagnosis and
carry out periodic outpatient evaluation of growth, development,
renal function, serum electrolytes, and response to therapy.
Monitoring
Patients initially need frequent outpatient follow-up care until the
metabolic abnormalities caused by the renal tubular transporter
mutation are stabilized with medications. The length of time to
stability depends on the severity of the mutation and the degree of
patient compliance.

53. Renal Transplantation



Bartter and Gitelman syndromes, by themselves, do
not lead to chronic renal insufficiency; however, in
patients with these syndromes who develop endstage renal disease (ESRD) for other
reasons, transplants from living relatives are an option
and result in normal urinary handling of
sodium, potassium, calcium, and magnesium.
Reports of renal transplants from living relatives in
ESRD patients with Bartter syndrome suggest that
many endocrinologic abnormalities in Bartter
syndrome improve or normalize after transplantation.
Because the genetic abnormality in Bartter syndrome
may be found only in the kidneys (which is certain in
Na-K-Cl cotransporter but may not be the case for
some of the other mutations), transplantation corrects
the problem by replacing unhealthy kidneys with
normal ones

54. Preemptive Surgery

One approach to the management of severe
Bartter syndrome involves preemptive
nephrectomy and renal transplantation.[30] The
rationale for this approach lies in the fact that
Bartter syndrome is an incurable genetic
disease, and the poorly controlled forms may
result in frequent life-threatening episodes of
dehydration and electrolyte imbalances.
Preemptive bilateral nephrectomies and
successful kidney transplantation prior to the
onset of ESRD has resulted in correction of
metabolic abnormalities and excellent graft
function.

55. Diet and Activity



Diet
Adequate salt and water intake is necessary to
prevent hypovolemia, and adequate potassium
intake is essential to replace urinary potassium
losses. Patients should consume foods and
drinks that contain high levels of potassium
(eg, tomatoes, bananas, orange juice).
With growth retardation, adequate overall
nutritional balance (protein-calorie intake) is
important. Whether other dietary supplements
(eg, citrate, magnesium, vitamins) are helpful
is not clear.

56. Activity

No restriction on general activity is
required, but precautions against
dehydration should be taken. Patients
should avoid strenuous exercise
avoided because of the danger of
dehydration and functional cardiac
abnormalities secondary to potassium
imbalance.

57. Prognosis





early diagnosis and appropriate treatment
may improve growth and neurointellectual
development.
sustained hypokalemia and
hyperreninemia can cause progressive
tubulointerstitial nephritis, resulting in endstage-renal disease.
With early treatment of the electrolyte
imbalances the prognosis is good.
Bone age is appropriate for chronological
age, and pubertal and intellectual
development are normal with treatment.
The disease does not recur in the patient
with a transplanted kidney.

58. References
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2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
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