| Abstract|| |
Gitelman's syndrome is an autosomal recessive renal tubular disorder characterized by hypomagnesemia, hypokalemia, hypocalciuria, and metabolic alkalosis. Hypocalcemic tetany as a presentation of Gitelman's syndrome has rarely been reported in literature. We report a rare case of Gitelman's syndrome presenting with hypocalcemic tetany along with hypokalemic periodic paralysis. A 17-year-old female was admitted to our hospital with a history of perioral numbness and carpal spasms of five days duration with progressive quadriparesis developing over a period of few hours. Past history was significant for three episodes of transient lower limb weakness. On examination, blood pressure was 110/70 mm Hg. Chvostek's sign and Trousseau's sign were positive. Neurologically, she was fully oriented. She had Grade 3 power in all the four limbs with intact sensation. Laboratory tests showed hypocalcemia (7.8 mg/dL), hypokalemia (2.2 mEq/L), hypomagnesemia (0.9 mEq/L), and hypocalciuria (104 mg/day). Arterial blood gas showed mild metabolic alkalosis with respiratory compensation. Thus, a clinical diagnosis of GS was made. The patient made a remarkable recovery after the correction of electrolyte imbalance. The aim of this case report is to re-emphasize the fact that hypocalcemia can rarely occur in Gitelman's syndrome.
|How to cite this article:|
Gandhi K, Prasad D, Malhotra V, Agrawal D. Gitelman's syndrome presenting with hypocalcemic tetany and hypokalemic periodic paralysis. Saudi J Kidney Dis Transpl 2016;27:1026-8
|How to cite this URL:|
Gandhi K, Prasad D, Malhotra V, Agrawal D. Gitelman's syndrome presenting with hypocalcemic tetany and hypokalemic periodic paralysis. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2020 Dec 2];27:1026-8. Available from: https://www.sjkdt.org/text.asp?2016/27/5/1026/190881
| Introduction|| |
Gitelman's syndrome is an autosomal recessive salt-losing renal tubulopathy which is characterized by hypomagnesaemia, hypocalciuria, and secondary aldosteronism, leading to hypokalemia and metabolic alkalosis.  The prevalence of Gitelman's syndrome is approximately 1 in 40,000.  It most commonly presents with muscle weakness, fatigue, and characteristic electrolyte abnormalities. Serum calcium levels are usually normal in Gitelman's syndrome. However, there have been few sporadic case reports describing hypocalcemia in Gitelman's syndrome which were attributed to disturbances in parathyroid hormone (PTH) metabolism due to chronic hypomagnesemia.
Here, we present a case of a young girl presenting with hypocalcemic tetany with concomitant hypokalemic periodic paralysis.
| Case Report|| |
A 17-year-old female presented to us with a history of perioral numbness and carpopedal spasms of one week duration followed by progressive weakness of all the four limbs and muscle cramps which developed over a period of few hours. Past history was significant for three episodes of transient lower limb weakness in the past four years which were attributed to hypokalemia that readily subsided following giving her parenteral potassium chloride; however, the cause of hypokalemia was never investigated. There was no family history of similar episodes. She denied any history of drug use including diuretics or laxative or self-medication. Birth history and developmental milestones were unremarkable. On physical examination, her blood pressure was within normal range without postural changes (110/70 mm Hg). Chvostek's and Trousseau's signs were positive. Her clinical and neurological examinations revealed Grade 3 quadriparesis without sensory loss. Higher mental functions and cranial nerve examination were normal. Deep tendon reflexes were normal. Other systemic examination was unremarkable. Biochemical findings are shown in [Table 1]. Arterial blood gas analysis showed metabolic alkalosis: pH 7.56, HCO  −29.5, and base excess +5.8. Complete blood picture, erythrocyte sedimentation rate, random blood glucose, serum creatinine, liver function tests, thyroid profile, rheumatoid factor, C-reactive protein, and anti-nuclear antibodies were within normal limits. Ultrasound imaging of kidneys was normal. Urine pH was 7.5 and specific gravity was 1.010.
She was provisionally diagnosed as a case of Gitelman's syndrome based on her clinical and biochemical findings.
Hypokalemia was treated with oral potassium chloride solution of 40-100 mEq/L/day, divided into three doses. Hypocalcemia was initially treated with intravenous 10% calcium gluconate over 10 min followed by an IV infusion of 50 mL of 10% solution in 500 mL normal saline over 4 h. Oral calcium supplementation was started at a dose of 1000 mg of elemental calcium daily. Hypomagnesemia was treated with intravenous magnesium sulfate administered 2 g 6 hourly with close monitoring of deep tendon reflexes followed by oral magnesium salts. Spironolactone 100 mg in two divided doses was also added. By day 3, the patient's symptoms had improved dramatically. Serum potassium and magnesium levels were corrected to 3.6 mEq/L and 1.9 mEq/L, respectively. Serum calcium was corrected to 8.6 mg/dL.
| Discussion|| |
Differential diagnosis for muscle weakness and tetany is large. On initial presentation, we kept the possibility of electrolyte disturbance, thyroid disorder, and inflammatory muscle disease, channelopathy, Vitamin D deficiency, and hypoparathyroidism. We investigated our patient according to our differential diagnosis. Investigations revealed that the patient had normal thyroid function, normal creatinine phosphokinase, normal 25 hydroxy Vitamin D, and parathyroid hormone (PTH) level. Based on the findings of hypokalemia, hypomagnesemia, hypocalcemia, and metabolic alkalosis, we narrowed our differential diagnosis to Barter or Gitelman's syndrome. Subsequently, urine finding revealed hypocalciuria and thus, a diagnosis of Gitelman's syndrome was made. Because of the unavailability of genetic testing, we could not confirm our diagnosis, which was the limitation of this case. Bartter's syndrome or Gitelman's syndrome should be considered in differential diagnosis in patients presenting with hypomagnesemia, hypokalemia, and metabolic alkalosis. Gitelman's syndrome is an inherited autosomal recessive, renal tubular disorder caused by inactivating mutation in the SLC12A3 gene that encodes the thiazide-sensitive sodium chloride cotransporter.  This condition is characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria.  GS is almost always associated with severe hypomagnesemia in 100% of the cases. Usually, serum calcium levels are normal in Gitelman's syndrome, and tetany is due to hypomagnesemia.  Because of the presence of concomitant hypocalcemia, we also considered BS in the differential diagnosis since mild hypomagnesemia is present in 20- 30% cases of Barter syndrome, possibly due to loss of transepithelial difference across ascending loop of Henle.  However, hypocalciuria in our patient was more suggestive of Gitelman's syndrome.
Hypocalcemia in this patient in spite of hypocalciuria could be explained due to either decreased PTH secretion secondary to persistent hypomagnesemia or end organ resistance to Vitamin D and PTH. 
| Conclusion|| |
Through this case report, we want to reemphasize Gitelman's syndrome as a differential diagnosis in patients presenting with hypokalemic tetany, and a correct interpretation of laboratory tests could be instrumental in excluding the other causes of hypocalcemia.
Conflict of interest: None declared.
| References|| |
Gitelman HJ, Graham JB, Welt LG. A new familial disorder characterized by hypokalemia and hypomagnesemia. Trans Assoc Am Physicians 1966;79:221-35.
Ji W, Foo JN, O'Roak BJ, et al. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat Genet 2008;40:592-9.
Simon DB, Nelson-Williams C, Bia MJ, et al. Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Nat Genet 1996;12:24-30.
Das SK, Ghosh A, Banerjee N, Khaskil S. Gitelman's syndrome presenting with hypocalcaemia, basal ganglia calcification and periodic paralysis. Singapore Med J 2012;53: e222-4.
Desai M, Kolla PK, Reddy PL. Calcium unresponsive hypocalcemic tetany: Gitelman syndrome with hypocalcemia. Case Rep Med 2013;2013:197374.
Anast CS, Winnacker JL, Forte LR, Burns TW. Impaired release of parathyroid hormone in magnesium deficiency. J Clin Endocrinol Metab 1976;42:707-17.
Department of Nephrology, Sawai Man Singh Hospital, Jaipur, Rajasthan