Gitelman’s Syndrome in Pregnancy With Adverse Foetal Outcome: A Case Report

Gitelman’s syndrome (GS) is a disorder characterized by hypokalaemia, hypomagnesemia, hypocalciuric and metabolic alkalosis. Despite the fact that it affects women of child-bearing age, only limited information is available regarding its impact on maternal and foetal outcome. We present the case of an un-booked and un-investigated 23-year-old primigravida who presented with chief complaints of vomiting and loose stools. The patient also complained of absent foetal movements in the last 12 hours. Investigations revealed hypokalaemia and hypomagnesemia and ultrasound revealed intra-uterine foetal demise. The patient was symptomatically relieved after electrolyte correction. Scarce reports on Gitelman’s syndrome in pregnancy have been documented with the majority of cases showing positive outcomes for the foetus. We hereby present a report of a primigravida with Gitelman’s syndrome and foetal loss which is considered uncommon.


Introduction
Maintaining an electrolyte as well as fluid balance is a necessity for a successful pregnancy. Disturbance in fluid and electrolyte balance has been related to an upsurge in the chances of morbidity and mortality, particularly among the elderly [1]. Dehydration can be caused by a variety of factors, including Gitelman's syndrome, which is discussed in detail here.
Gitelman's syndrome (familial hypokalaemia-hypomagnesemia) is characterized by hypokalaemic metabolic alkalosis, hypomagnesemia, and inadequate urinary calcium excretion. It is a relatively prevalent but overlooked cause of hypokalaemia. It is a hereditary renal tubular illness with an incidence of 1-10/40,000 [2], that was initially discovered in 1966 [3,4]. It might be because of the inactivation of mutations in the SLC12A3 gene, which codes for the apical sodium chloride cotransporter and is found on chromosome 16 (16q13), leading to salt wasting, hypokalaemia, alkalosis, and hypocalciuria [5]. As a result of increased sodium delivery to the cortical collecting duct, sodium reabsorption by the epithelial sodium channel increases, which is counterbalanced by potassium loss, resulting in hypokalaemia.
The increased distal exchange of magnesium ions for sodium ions causes hypomagnesaemia. Salt cravings, exhaustion, and postural hypotension are all common symptoms of this condition. Gitelman's syndrome has been related to a higher chance of miscarriage as well as Intra Uterine Growth Restriction (IUGR) during pregnancy along with significant maternal morbidity due to electrolyte imbalance concerns [6][7][8][9].

Case Presentation
A 23-year-old primigravida at 37 weeks period of gestation, un-booked and un-investigated, presented to the emergency with chief complaints of absent fetal movements in the last 12 hours, vomiting for five days (5-6 episodes per day), loose stools for three days, itching over palms and soles for two weeks. Her vitals were normal with a mild degree of fever. There was no jaundice. Abdominal findings revealed no focal tenderness or guarding, the uterus was relaxed and corresponding to 36 weeks period of gestation, cephalic presentation, and on auscultation, the foetal heart sound could not be localized clinically. Per vaginal examination was done and the patient was found to be in the latent phase of labour.
Laboratory examination including a complete haemogram, kidney and liver function test, and urine analysis was performed. Arterial blood gas revealed pH 7.5, pCO2 43 mm of Hg, Na+ 135 mEq/L, K 1.92 mEq/L, chloride 99 mEq/L, bicarbonate 31.7 mmol/L. The electrocardiogram revealed PR interval prolongation of 0.24 seconds, flat t waves, and prominent U waves. Her serum potassium level was 2.5 mEq/L, and her serum Mg level was 1.2 mEq/L, according to her first chemistry panel ( Table 1). 1 1 1  Her ultrasound revealed a single intrauterine foetus of 34 weeks 6 days with absent cardiac activity suggestive of intra-uterine foetal demise. Injectable ondansetron was used to reduce nausea and vomiting, and racecadotril was used to manage loose stools, but electrolyte imbalances were critically low despite the recovery of hyperemesis. The first line of treatment was intravenous (IV) isotonic saline and parenteral potassium. Labour induction of intra-uterine fetal demise was done using two doses of cerviprime gel six hours apart, followed by two doses of tablet misoprostol 50 mcg four hours apart. The patient was then taken up for emergency lower segment cesarean section (LSCS) in view of obstructed labour. Serum potassium level was checked continuously during her hospitalisation (  This patient was readmitted many times during her first trimester of pregnancy for recurrent nausea and vomiting, each time with severe hypokalemia and hypomagnesemia, and her care was continued according to the previous plan. She was relatively asymptomatic except for nausea and emesis, and she denied muscle cramps, weakness, palpitations, or syncopal attacks.

Discussion
Renal potassium wasting is promoted by physiological changes during pregnancy, while blood potassium level is controlled in the physiologic array due to an increase in progesterone level that opposes kaliuresis. This compensatory mechanism is rapidly overcome in the presence of Gitleman syndrome, resulting in severe hypokalemia.
Maintenance of fluid balance in pregnant women with Gitleman syndrome might be a challenging task. Despite various physiological changes, such as volume expansion, increased renal blood flow, increased glomerular filtration rate (GFR), and activation of the renin-angiotensin-aldosterone axis, that contribute to renal potassium squandering during pregnancy, potassium homeostasis typically remains normal. Increased progesterone levels, which fight kaliuresis, maintain normal serum potassium levels [5].
As was the case in our instance, moderate diarrhoea, vomiting, and pregnancy are common precipitating events. An ideal environment for the development of severe symptomatic hypokalaemia is created in pregnancy by the surge in demand for magnesium and potassium accompanied by increased urine loss. The typical finding of hypomagnesaemia along with metabolic alkalosis, hypokalaemia, hypocalciuria, and hypermagnesuria in 24-hour urine samples serves as the basis for the diagnosis. Genetic testing and the identification of the SCL12A3 gene mutation are the sole methods for diagnosing this condition [10].

Conclusions
Gitelman syndrome in pregnancy is a common but overlooked cause of hypokalemia in pregnancy which can have a grave effect on the fetomaternal outcome. Due to its varied presentations, it is often misdiagnosed and hence not appropriately managed. Gitelman's syndrome diagnosis must be made with a valid index that is very accurate, followed by meticulous monitoring and aggressive care, for a better prognosis of the mother and the foetus.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.