gitelman syndrome ( gs ) is a rare autosomal - recessive inherited disorder with 99% penetrance caused by inactivating mutations in the slc12a3 gene , localized on the 16q13 chromosome .
this genetic defect impairs the function of the thiazide - sensitive sodium - chloride cotransporter in the distal convoluted renal tubule .
gs is the hypocalciuric , hypomagnesemic variant of bartter syndrome , which was first described in 1966 .
, we describe the management and pregnancy course of a 27-year - old patient with gs .
we report the course of a pregnancy in a 27-year - old woman previously diagnosed with gs . her pregnancy was uneventful and she remained asymptomatic despite persistent hypokalemia .
potassium levels were followed at a regular basis and ranged between 2.3 and 3.1 mmol / l ( 2.3 and 3.1 meq / l ) .
she was electively admitted to hospital at 39 weeks of gestational age for full - term induction of labor .
the patient received 240 meq of intravenous potassium chloride and 180 meq per oral , as well as 4 g of intravenous magnesium sulfate and 1200 meq of oral magnesium oxide .
she was continued on 150 mg daily of eplerenone . despite aggressive electrolyte replacement , her potassium and magnesium levels ranged between 2.0 and 3.0
meq / l ) and 1.1 and 2.6 mmol / l ( 1.1 and 2.6 meq / l ) , respectively .
the baby was born healthy with 2863 g , and apgar measurements were 8 and 9 at 1 and 5 min , respectively .
first described in 1966 by gitelman et al . , gs is a rare autosomal - recessive condition characterized by hypokalemia , metabolic alkalosis and hypomagnesemia .
it has since been shown to result from a mutation in the slc12a3 gene on chromosome 16 leading to a loss of function mutation in the sodium - chloride cotransporter in the distal convoluted tubule .
this leads to potassium and magnesium wasting into the cortical collecting duct as the increase in delivered sodium is reabsorbed through the epithelial sodium channel . despite being normotensive
 aldosterone axis . to date , 24 pregnancies in 18 women with gs have been described in the literature [ 315 ] .
twenty of the pregnancies had no reported fetal complication ( table 1 ) , six pregnancies were complicated by oligohydramnios [ 5 , 8 , 9 , 12 , 13 ] and one was complicated by intrauterine growth retardation .
kaliuresis does not typically ensue presumably due to the antimineralocorticoid effects of progesterone demonstrated by ehrlich and lindheimer in 1972 .
de haan et al . have suggested that this protective mechanism may be impaired in gs patients thus resulting in an exacerbation of potassium and magnesium losses .
the increase in the requirement for oral potassium during pregnancy has been documented by several authors including talaulikar et al . in 2005 who reported a 6-fold increase in potassium and magnesium requirements in their patient .
mmol / l ( 3.64.0 meq / l ) range [ 10 , 14 ] .
it has been suggested that normalization of potassium and magnesium levels is not required for a good obstetric and neonatal outcome .
worsening of the symptoms of gs such as fatigue , cramping , tetany and dizziness has been described in the gs pregnancies [ 7 , 12 , 13 ] .
the symptoms may be exacerbated by hyperemesis and fetal demand for potassium [ 9 , 12 ] .
worsening of symptoms is cited as a reason for the modification of therapy [ 3 , 4 , 611 , 13 ] .
our patient did not exhibit symptoms during her pregnancy , and we felt that intravenous potassium loading would be inefficient and unnecessary in the absence of symptoms . beyond the use of supplemental cations , the management of patients with gs has included the use of potassium - sparing diuretics .
the us food and drug administration has deemed spironolactone a category c drug in pregnancy .
this is consistent with the findings of mascetti et al . who describe a series of spironolactone - exposed children born to a group of mothers with bartter syndrome , another potassium - wasting nephropathy .
the use of amiloride and eplerenone , both class b drugs in pregnancy , has been previously documented in gs [ 4 , 9 , 14 , 15 ] .
in contrast to bartter syndrome , the use of non - steroidal anti - inflammatory drugs ( nsaids ) to inhibit prostaglandin synthase is theoretically of no benefit as gs is not a hyperprostaglandinemic state .
angiotensin - converting enzyme inhibitors are contraindicated in pregnancy due to teratogenic effects as well as impaired fetal growth
. there has been a concern over the potential for a ventricular tachyarrhythmia during pregnancy and childbirth due to hypokalemia .
fortunately , no such complication has been observed in any of the documented gs pregnancies .
the extensive work of calo et al . in this area suggests however that the upregulation of the nitric oxide system and vasodilation seen in gs may limit the physiologic response to increased myocardial demand [ 19 , 20 ] .
it is also suggested in subsequent work that increased angiotensin 17 levels seen in gs may be antiarrhythmic at low levels and proarrhythmic at very high levels .
the small number of documented gs pregnancies precludes any rigorously studied recommendations for management in the peripartum period .
the anesthesia literature describes a risk of complications in gs patients in the perioperative setting .
these include electrocardiographic changes as well as vasodilation , electrolyte imbalance and alkalemia complicating the ventilatory management of the patient .
given the expected physiologic demands of labor and delivery , it appears that an elective , multidisciplinary approach to the delivery of the child is most prudent .
baseline electrocardiography should be obtained as up to 50% of patients with gs have qt interval prolongation .
frequent monitoring of electrolytes is advisable as is blood pressure monitoring given the propensity of gs patients have vasodilation .
the postpartum period is associated with natriuresis ; however , this would not explain a drop in potassium during active labor .
it may be , however , that the drop in serum potassium observed here is related to a shift in potassium from the extracellular to intracellular space as could be seen in any patient and is not unique to gs . in our patient
pretreatment with a thiazide diuretic was associated with a more significant drop in serum potassium during epinephrine loading than that seen in the control group receiving epinephrine alone .
as gs mimics the effects of thiazide diuretics , one could assume a similar effect in these patients .
table 1.summary with the cases of gitelman syndrome during pregnancyauthorage at diagnosis ( years)diagnosismaternal age ( years)number of patientsnumber of pregnanciessymptomsjones jm et al .
17before pregnancy1 ) 24131st- asymptomatic except for tiredness in 3rd trimester2 ) 252nd- asymptomatic3 ) 273rd- asymptomatictalaulikar gs et al .
20before pregnancy1 ) 22121 ) increasing tiredness , muscle cramps . required 3 hospitalizationskwan et al . 2 )
n / abefore pregnancy1 ) 24211st- symptomatic , not specified2 ) 272nd- muscle weakness , fatiguede arriba g et al .
201st trimester ( 10 weeks)2011tiredness , muscle weakness , decreased muscle strength and tenderness bilaterally in lower extremitiesmccarthy fp et al .
n / an / a1 ) 27561 , 2 , 3 , 4 ) uneventful 5 ) tiredness and tetanic seizures2 ) 323 ) 284 ) 335 ) 33/35calo la et al .
meq / l1.3 meq / lk and mg supplementationoligohydramniosinduced vaginal deliveryhealthy female infant , 2410 g36 weeksn / an / ak and mg supplementation1 , 2 and 3 ) none1st- spontaneous labor1st- healthy male infant .
2620 g1st-35 weeks1st- k range = 2.32.8 mmol / l1st- mg range = 0.530.58 mmol / l1st- k and mg supplementation2nd- spontaneous labor2nd- healthy female infant , 2910 g2nd- 38 weeks2nd- maximum level = 3.1 mmol / l2nd- maximum level = 0.56 mmol / l2nd- k and mg supplementation3rd - spontaneous labor3- healthy female infant .
n / a3rd- n / a3rd - n / a1 ) nonenormal deliveryhealthy infant1 ) n / ak range = 2.33.4 mmol / l1 and 2)n / a1 and 2 ) k and mg supplementation2 ) gestational diabeteselective c - sectionn / a2 ) 39 weeksn / anoneuncomplicated vaginal delivery , induced for post - term pregnancyhealthy female infant , 3250 g41 weeks and 4 daysn / an / ak and mg supplementation1st - oligohydramnios , partial placenta previa , intrauterine growth restriction.1st- primary c - section , healthy infanthealthy female infant , 3970 g1 and 2 ) 38 weeksn / an / ak and mg supplementation .
healthy infanthealthy male infant , 3845 goligohydramniosprogrammed c - section , w / o complicationshealthy infant , 3000 gn / a2.42.8 meq / ln / ak and mg supplementation , spironolactone.oligohydramnioselective c - section ( breech presentation)healthy female baby , 3350 g273maximum level = 3.0 mmol / lmaximum level = 0.68 mmol / lk and mg supplementationoligohydramniosinduced c - section ( failure to progress in the first stage)healthy female baby , 2940 g266k range = 2.63.3 mmol / lmg range = 0.470.66 mmol / lk and mg supplementation , amiloride .
supplementation of k and mgfetal macrosomia ( patient had gestational diabetes)induced c - sectionhealthy male baby , 3080 gn / an / an / ak and mg supplementation , amiloride ( 1st trimester ) .
supplementation of k and mg.nonevaginal deliveryhealthy female baby , 3630 g2732.62.9 mmol / ln / aepleronone1 , 2 , 3 , 4 and 5 ) nonen / ahealthy male baby .
4080 g40 weeksn / an / ak and mg homeopathy k , amiloride k , mg none ( 1st pregnancy ) / k ( 2nd pregnacy)healthy female baby , 3380 g38 weekshealthy female baby , 2420 g37 weekshealthy male baby .
2810 g41 weekshealthy male baby , 2830 g / healthy male baby , 2640 g38 weeks/36 weeks1 and 2 ) nonen / ahealthy female baby 2900 gat termn / an / a1 and 2 ) k and mg supplementationhealthy female baby 3125 g / healthy female baby 3400 gat term / at term summary with the cases of gitelman syndrome during pregnancy in conclusion , the experience of clinicians treating pregnant women with gs is limited but is also being described with more frequency .
there is no evidence of significant risk to the fetus but maternal symptoms may worsen during the pregnancy .
the management of gs should be focused on the replacement of potassium and magnesium though routine intravenous supplementation and should be reserved for cases of worsened symptoms .
cautious use of adjunctive treatment with potassium - sparing agents should be considered as the potassium requirement may increase significantly during pregnancy .
in addition to gs - related potassium and magnesium loss , hypokalemia can be exacerbated by cellular shift as well as extrarenal losses of cations which can affect any patient .
no consensus recommendations exist for the perinatal management of the pregnant gs patient but an elective delivery in a setting with appropriate cardiac monitoring and central venous access is prudent as potassium and magnesium aberrations during active labor may be seen .
 gitelman syndrome ( gs ) is an autosomal - recessive condition characterized by hypokalemia , hypomagnesemia and hypocalciuria . 
 very little information is available in the literature to guide the management of pregnant patients with gs . 
 we report a case of a 27-year - old woman with gs who became pregnant and despite persistent hypokalemia and hypomagnesemia during pregnancy and labor , had a successful maternal and fetal outcome . 
Introduction
Case presentation
Discussion
Conflict of interest statement