Mudassir Ali1, Muhammed Pervez1, Shafie Kamaruddin1, Praveen Partha1, Giridhar Tarigopula1, John Sayer2, Paul Peter1 1Darlington Memorial Hospital, 2Institute of Genetic Medicine, Newcastle University
Gitelman syndrome (GS) is a rare autosomal recessive renal disorder resulting from a mutation in the gene SLC12A3, which encodes for the thiazide‐sensitive sodium chloride co-transporter in the distal convoluted tubule. It is characterized by hypokalaemia, hypomagnesaemia, hypocalciuria, metabolic alkalosis, and normal or low blood pressure. Many symptoms of this rare renal disorder are related to these electrolyte abnormalities, and adversely affect the patient’s quality of life. We report a case of GS in pregnancy with episodes of symptomatic hypokalaemia requiring multiple hospital admissions for electrolyte replacement. (1)(2)
A 27 years old lady who was known to have hypokalaemia since she was 17 years of age, presented to hospital in December, 2017 with symptomatic hypokalaemia complaining of tingling and numbness around her mouth and weakness of both lower limbs. This was her first admission in hospital related to hypokalaemia and the potassium was 2.2 mmol/L and magnesium was 0.6 mmol/L, she was found to be pregnant at this admission. Prior to this admission she was just on oral potassium citrate syrup 5 ml BD.
She received intravenous potassium and magnesium infusion and was discharged on oral supplements. Later in January 2018 she had miscarriage at 15 weeks. In December, 2018 she had another miscarriage at 11 weeks.
Between February to July 2018 she had monthly at-least once hospital admission for iv potassium and magnesium infusion. After July 2018 she required weekly intravenous potassium infusion about 80-160 mmol of KCL per admission and continued to have hospital admission once or twice a week for electrolyte replacement. Following informed consent, DNA analysis revealed two heterozygous pathogenic SLC12A3 variants c.334G>T, p.(Glu112Ter); c.2883+1G>T, confirming a molecular genetic diagnosis of GS.
She later became pregnant, making the management more challenging. Currently she is in her third trimester and this is her first pregnancy which came so far and hopefully she would have successful delivery of baby. Her current medications include oral amiloride 5 mg BD, potassium chloride 600 mg MR 5 tablets QDS, magnesium glycerophosphate 4 mmol BD and sodium tablets slow release 1200 mg TDS. She is under regular care of endocrinologist and nephrologist with special interest in renal genetics.
After miscarriage, the symptoms of GS often improve and patients have stable levels of potassium. Our case presents an unusual example where patient had resistant severe symptomatic hypokalaemia which persisted beyond her miscarriage, even on maximum tolerated therapy. Also this case highlights with multidisciplinary approach and close monitoring of potassium and other electrolytes, with adjustment of the individualised oral electrolyte replacement therapy such patients could have successful pregnancy outcomes.
A randomized controlled study (3) was performed in patients with GS providing evidence of efficacy of treatment with three drugs (Indomethacin, amiloride and eplerenone). Although these drugs have different mechanisms of action, they all increase plasma potassium concentration on the short term basis. Additional studies are needed to address the long-term efficacy and tolerability of these treatment options
In general, GS is a chronic condition that is usually manageable. However, as in our case severity of GS may seriously hamper daily activities and effect quality of life. The main aim is to correct electrolyte abnormalities, improve quality of life and prevent life threatening complications like ventricular arrhythmias and cardiac arrest.
- Physicians need to be aware of such challenging cases of GS which could get worse post miscarriage.
- Need to be aware that patients with GS and pregnancy and very challenging to manage. In our case the patient was very keen to get pregnant
- The priority should be to keep patient safe, improve quality of life and prevent complications in general. In special cases like ours having successful pregnancy is also vital while keeping patient safety.
- Moustakakis MN, Bockorny M. Gitelman syndrome and pregnancy. Clin Kidney J [Internet]. 2012 Dec 1;5(6):552–5. Available from: https://academic.oup.com/ckj/article-lookup/doi/10.1093/ckj/sfs126
- Blanchard A, Bockenhauer D, Bolignano D, Calò LA, Cosyns E, Devuyst O, et al. Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int [Internet]. 2017 Jan;91(1):24–33. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0085253816306020
- Blanchard A, Vargas-Poussou R, Vallet M, Caumont-Prim A, Allard J, Desport E, et al. Indomethacin, Amiloride, or Eplerenone for Treating Hypokalemia in Gitelman Syndrome. J Am Soc Nephrol [Internet]. 2015 Feb;26(2):468–75. Available from: http://www.jasn.org/lookup/doi/10.1681/ASN.2014030293