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Pregnancy outcome in a patient with Gitelman’s syndrome-a case studyDr. Gabriel Onyeka Ekekwe, Mrs. Sandhya RaoSt Helens & Knowsley Teaching Hospitals NHS

Whiston Hospital, Warrington Road, Prescot, L35 5DR

IntroductionGitelman’s syndrome is a rare autosomal recessive renal tubulopathyIt was first described by Gitelman in 1966 (Riveira-Munoz et al, 2007) It is caused by mutation in SLC12A3 gene that encodes thiazide-sensitive sodium chloride co-transporter in the distant convoluted tubules (Adam et al, 2011; Hollenberg, 2011)It is characterised by hypokalaemia, hypomagnesaemia, secondary hyperaldosteronism, metabolic alkalosis and hypocalciuriaIt usually manifests in adolescent or adulthood and are often asymptomatic.It may present with muscle weakness/pain, fatigue, dizziness, nocturia, polydipsia, polyuria, paraesthesia, palpitations, low blood pressure, and rarely blurring of vision, vertigo, ataxia, tetany and seizure (Riveira-Munoz et al, 2007)The case report presented highlighted the following;i.Management issues regarding Gitelman’s syndrome in pregnancyii.Areas of controversy in the management of this rare condition. Only 12 cases has been described in the literatures (Adam et al, 2011)iii.The need for high index of suspicion in making the diagnosis in pregnancy and also early initiation of appropriate management in order to avoid morbidities and possibly mortality

Case Report23 year old G2P1 whose first pregnancy was in 2007It was complicated with hypokalemia which was attributed to poor diet and recurrent urinary tract infectionShe was managed with oral potassium and magnesium supplements and long term antibioticHad vaginal delivery at 37 weeks following induction of labour due to pre-eclampsia Was admitted to the coronary unit with severe chest pain at 12 weeks gestation in her second pregnancyShe was found to have low potassium (3.1mmol/L), urinary potassium and calcium were high. ECG did show any changesThere no history of diarrhoea , vomiting or laxative use

ReferencesAdam, M., Panitz, B. and Adam, B (2011) ‘Eplerenone for Gitelman Syndrome in Pregnancy’, Nephrology vol. 16; pp. 349-350. Available from: doi: 10.1111/j.1440-1797.2010.01396.xBasu, A., Dillion, R.D.S., Taylor, R., Davison, J.M. and Marshall, S.M. (2004) ‘Is normalisation of serum potassium and magnesium always necessary in Gitelman’s Syndrome for a successful obstetric outcome? International Journal of Obstetrics and Gynaecology vol. 111: pp. 630-634.Bennett, P. and Williamson, C. (2010) ‘Basic Science in Obstetrics and Gynaecology-A textbook for MRCOG Part 1, 4th edition. London: Churchill Livingstone.De Arriba, G., Sanchez-Heras, M. and Basterrechea, M.A. (2009) ‘Gitelman’s Syndrome during pregnancy: a therapeutic challenge’, Arch. Gynecol Obstet. 280:807-809 Available from: doi: 10.1007/s00404-009-0994-3Hollenberg, N.K. (2011) ‘Improving genetic testing for Gitelman’s syndrome’, Curr. Hypertens Rep [Online] Available from: doi: 10.1007/s11906-011-0213-z Kwan, T.K. and Falk, M.C. (2010) ‘Second pregnancy outcome in a patient with Gitelman syndrome without the use of parenteral electrolyte supplementation’, The Royal Australian and New Zealand College of Obstetricians and Gynaecologists vol. 51; pp. 91-95 Available from: doi:10.1111/j.1479-828X.2010.01248.xMcCarthy, F.P., Magee, C.N., Plant, W.D. and Kenny, L.C. (2010) ‘Gitelman’s syndrome in pregnancy: case report and review of the literature’, Nephrol. Dial. Transplant, vol. 25:1338-1340 Available from: doi: 10.1093//ndt/gfp688 Riveira-Munoz, E., Chang, Q., Bindels, R.J. and Devuyst, O. (2007) ‘Gitelman’s syndrome: towards genotype-phenotype correlations? Padiatr. Nephrol. Vol. 22:326-332 Available from: doi: 10.1007/s00467-006-0321-1

Diagnosis of heterozygous Gitelman,s syndrome was made via genetic testing at 24 weeks gestationShe was managed with potassium and magnesium supplements, amiloride with favourable pregnancy out comeHad serial growth USS which showed normal fetal growth and liquor volumeShe was admitted on three different occasions and treated with intravenous potassium when serum potassium was found to 2.4mmol/L on each occasionsShe was induced at 37 weeks due to persistently potassiumHad an uneventful vaginal delivery of a health babyShe was co-managed with physicians-Nephrologist and EndocrinologistWas commenced on Microgynon for contraception 3 months post deliveryThe OCP was however discontinued on the advice of the endocrinologist as it worsened the salt losing condition

DiscussionsNormal pregnancy is associated with up to 70% and 50% increase in renal blood flow and glomerular filtration respectively (Bennett and Williamson, 2010) Compensatory increase in tubular reabsorption maintain maternal electrolytes despite the increase in renal blood flow and glomerular filtration in pregnancy (Bennett and Williamson, 2010)This compensatory mechanism is disrupted in patients with Gitelman’s syndromeTherefore, pregnancy and use of combined oral contraceptive are capable of worsening electrolyte loss as was noted in our patient (Kwan and Falk, 2010)Diagnosis can be made with serum potassium and magnesium, and urinary potassium and calcium. Genetic testing remains the gold standard for definitive diagnosisOver a 100 mutations are scattered through SLC12A3 gene. Heterozygous individuals are not expected to be symptomatic in a recessively transmitted disease (Reveira-Munoz et al, 2007; Hollenberg, 2011)Our patient was heterozygous yet symptomatic. This may be explained by limitation of current genetic tests to identify the second mutant allele (Reveira-Munoz et al, 2007; Hollenberg, 2011

Wide variation in patients symptoms may due to genotype-phenotype correlation (Reveira-Munoz, 2007)Treatment with potassium and magnesium supplements, and potassium sparing diuretics like amiloride and spironolactone should be aimed mainly at symptomatic control rather than aggressive efforts to normalise potassium and magnesium levels (Kwan and Falk, 2010; McCarthy et al, 2010)Spironolactone found to be safe despite concerns of possible antiandrogenic effects on male fetus (De Arriba et al, 2009; Basu et al, 2004)Use of aldosterone antagonist is controversial and should be reserved as second line diuretic (De Arriba et al, 2009; Basu et al, 2004) Ultrasonic fetal and amniotic fluid surveillance is mandatory due possible adverse effects of the use of diuretics in pregnancy

ConclusionsThe diagnosis and appropriate management Gitelman’s syndrome in pregnancy is vital as pregnancy is capable of worsening the conditionAlso it constitutes significant general anaesthetic riskDespite the exacerbation of the condition in pregnancy, maternal and fetal outcomes remain favourable Treatment with potassium and magnesium supplements and potassium sparing diuretic are aimed at relieving worsening maternal symptomsUse of aldosterone antagonist in pregnancy remains controversial. It may be used as second line drug in patients intolerant to amiloride or spironolactone (first line drugs)Ultrasonic fetal and amniotic fluid surveillance is mandatoryCombined oral contraceptive should be avoided in these patientsThere need for more research to improve genetic testing methods for the syndrome .Research should also be conducted to correlate Gitelman’s genotypes with maternal and fetal outcome