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 Table of Contents  
CASE REPORT
Year : 2015  |  Volume : 7  |  Issue : 1  |  Page : 27-29

An adolescent with tingling and numbness of hand: Gitelman syndrome


Department of Pediatrics, Division of Nephrology, University of Florida, Gainesville, Florida, USA

Date of Web Publication27-Jan-2015

Correspondence Address:
Atul Poudel
Department of Pediatrics, Division of Nephrology, University of Mississippi Medical Center, Batson Children`s Hospital, 2500 N State Street, R-116A, Jackson, MS 39216
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1947-2714.150086

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  Abstract 

Context: Gitelman syndrome is an inherited autosomal recessive disorder. It is usually diagnosed incidentally during adolescence or early adulthood based on clinical and biochemical findings. Case Report: We present a case of 16 years old adolescent female presenting with recurrent chest pain, tingling, and numbness of bilateral hands. Diagnosis was established by the typical biochemical abnormalities with hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis, and hyperreninemic hyperaldosteronism. Genetic diagnosis was confirmed by sequence analysis of the SLC12A3 gene showing the compound heterozygous mutation encoding the thiazide-sensitive sodium chloride co-transporter. The patient was treated with oral potassium, magnesium, and amiloride with complete improvement of symptoms and biochemical profile. Conclusion: Gitelman syndrome should be considered as a differential diagnosis in work up of hypokalemia, especially in adolescent age group. The presence of hypokalemia, metabolic alkalosis, hypomagnesaemia, hypocalciuria, and mutation analysis provides the final diagnosis.

Keywords: Adolescent, Gitelman syndrome, Hyperrenineimic hyperaldosteronism, Hypokalemia


How to cite this article:
Poudel A. An adolescent with tingling and numbness of hand: Gitelman syndrome. North Am J Med Sci 2015;7:27-9

How to cite this URL:
Poudel A. An adolescent with tingling and numbness of hand: Gitelman syndrome. North Am J Med Sci [serial online] 2015 [cited 2019 Nov 21];7:27-9. Available from: http://www.najms.org/text.asp?2015/7/1/27/150086


  Introduction Top


Gitelman syndrome (GS) is an inherited renal tubular disorder characterized by hypokalemia, alkalosis, and hypertrophy of the juxtaglomerular complex with secondary hyperaldosteronism. [1] The mode of inheritance is autosomal recessive. Gitelman syndrome results from dysfunctional Na-Cl transporters in the distal convoluted tubule, which results in failure to conserve potassium and magnesium. [2] Secondary biological adaptations of downstream tubular segments in collecting ducts are responsible for alkalosis, renin-aldosterone activation, and prostaglandin hypersecretion. The first clinical presentation is usually observed during childhood or adolescence and may include transient episodes of weakness, paresthesia. The course of disease is generally mild, and some patients even remain asymptomatic.


  Case Presentation Top


A 16-year-old Asian American female presented to emergency room with numbness over all four extremities for 1 week. She had no history of medication usage, including diuretics and laxative. There was no history of developmental delays. Patient was attending ninth grade with average school performance. There was no family history of GS, developmental delays or malnutrition issues. Her height was at tenth percentile, weight at fifteenth percentile, and BMI at tenth percentile. Neurologic examination revealed no sensory or motor deficit. Other system examinations were found to be normal. Laboratory results showed hypokalemia (2.3 mmol/L), metabolic alkalosis (pH 7.48, and bicarbonate 33 mmol/L), and hypomagnesaemia (1.2 mmol/L). Further evaluation was initiated by pediatric nephrology service to find out cause of hypokalemia. Her supine plasma renin to be 25 ng/ml/hour (normal range, 2.47-2.23 ng/ml/hour), supine aldosterone 7.2 pg/ml (normal range, 1-16 pg/ml). The daily excretions of potassium and calcium were 99 mmol/day and 32.8 mg/day, respectively. The urine calcium/creatinine ratio was 0.04. She was treated with oral magnesium (900 mg/day), potassium (60 mmol/day) and amiloride 5 mg daily. Tingling and numbness of extremities resolved and potassium/ magnesium serum levels normalized (potassium 3.7 mmol/L and magnesium 1.8 mmol/L) within 7 days of treatment. Patient was discharged home on same daily doses of amiloride, potassium and magnesium supplementation. Genetic diagnosis was confirmed by sequence analysis of the SLC12A3 gene showing the compound heterozygous mutation encoding the thiazide-sensitive sodium chloride co-transporter.


  Discussion Top


The electrolyte abnormalities induced by thiazide diuretics and GS were found to be similar. The Na-Cl co-transporters (NCCT) are found to be dysfunctional in GS. [3],[4] Epidemiologic studies have demonstrated that there is no ethnic predilection for GS, and both sexes are equally affected. Simon et al. first demonstrated complete linkage of GS to the NCCT gene; human gene maps SLC12A3 on chromosome16q13 and specified GS as an autosomal recessive disorder with 99% penetrance. [3],[4],[5],[6] The defect in NCCT leads to sodium chloride (NaCl) wasting and hypovolemia, which stimulates the renin-angiotensin-aldosterone system, and causes an increase in apical Na reabsorption and stimulation of the basolateral Na-K-ATPase. The elevated aldosterone levels also stimulate H-ATPase pumps in the cortical and medullary collecting ducts, leading to increased apical H secretion. K and H excretion increases as K-enters from the basolateral membrane via the Na-K-ATPase pumps, resulting in hypokalemic metabolic alkalosis. Sodium reabsorption via sodium channels is accompanied by potassium and hydrogen ion excretion, resulting in further hypokalemia and metabolic alkalosis. NaCl uptake through the apical membrane decreases, whereas intracellular Na continuously leaves the cells through the Na-K-ATPase at the basolateral membrane. This extrusion of Na reduces intracellular Na concentration, thereby hyperpolarizing distal convoluted tubular cells and causing Ca2+ to enter the apical membrane through Ca2+ channels. [7] Similarly, loss of NCCT function can inhibit reabsorption of magnesium via an apical Na/Mg exchanger. Because distal convoluted tubules reabsorb approximately 5% of filtered magnesium and the reabsorption is load-dependent, [8] impairment in magnesium reabsorption in this segment would be expected to result in magnesium wasting and hypomagnesaemia.

Patients with GS do not have symptoms throughout infancy and the preschool years. They are often diagnosed in adolescence or early adulthood. This disorder may be diagnosed as an incidental finding during laboratory investigation in asymptomatic patients or patients with intermittent mild symptoms of muscle weakness, fatigue, cramps. Severe symptoms such as tetany, rhabdomyolysis, and paralysis have been reported. [9],[10],[11] In our case, patient was brought to the emergency room at the middle of night with acute severe tingling and numbness of hands. When elaborate past medical history was obtained after hospital admission; she reported mild intermittent tingling and numbness of hands for many years but never been reported to the primary care doctor. There were no additional factors in her case to explain acuteness of presentation. The most common reported symptoms were salt craving (95%), musculoskeletal symptoms such as cramps (84%), muscle weakness and aches (70%), and constitutional symptoms such as fatigue (82%), dizziness (80%), nocturia (80%), and polydipsia (65%). [11],[12] Almost all GS patients have hypokalemia, hypomagnesemia, metabolic alkalosis, and markedly reduced urinary calcium excretion. The ratio of urinary calcium to urinary creatinine less than 0.1. [11],[12]

GS is differentiated from Bartter syndrome by severity of clinical presentation and laboratory findings. [13] Patients with Bartter syndrome typically present before the age of 6 years with severe symptoms such as dehydration and growth retardation. Serum magnesium and urinary calcium findings distinguish GS from Bartter syndrome, with GS denoting the subset with hypomagnesemia and hypocalciuria. In addition, genetic analysis may further differentiate the two syndromes with complete linkage of GS to the locus encoding NCCT on chromosome 16q13. [13] The mainstay treatment for GS is oral potassium and magnesium supplementation. [13] The addition of potassium- sparing diuretics helps retrieving potassium loss from distal and collecting segment of renal tubules. Magnesium therapy not only corrects the hypomagnesaemia but also improves hypokalemia. [14],[15] Long-term prognosis for renal function and life expectancy is excellent in GS patients.

In conclusion, GS should be considered as a differential diagnosis in work up of hypokalemia, especially in adolescent age group. The presence of hypokalemia, metabolic alkalosis, hypomagnesaemia, hypocalciuria, and mutation analysis provides the final diagnosis.

 
  References Top

1.
Gitelman HJ, Graham JB, Welt LG. A new familial disorder characterized by hypokalemia and hypomagnesemia. Trans Assoc Am Physicians 1996;79:221-35.  Back to cited text no. 1
    
2.
Simon DB, Nelson WC, Bia MJ, Ellison D, Karet FE, Molina AM, et al. Gitelman's variant of Bartter's syndrome, inherited hypokalemic alkalosis,is caused by mutations in the thiazide-sensitive Na-Cl co-transporter. Nat Genet 1996;12: 24-30.  Back to cited text no. 2
    
3.
Obermuller N, Bernstein P, Velasquez H, Reilly R, Moser D, Ellison DH, et al. Expression of the thiazide-sensitive Na-CI cotransporter in rat and human kidney. Am J Physiol 1995;269:F900-10.  Back to cited text no. 3
    
4.
Plotkin MD, Kaplan MR, Verlander JW, Lee WS, Brown D, Poch E, et al. Localization of the thiazide sensitive Na-CI cotransporter, rTSC1, in the rat kidney. Kidney Int 1996;50: 174-83.  Back to cited text no. 4
    
5.
Pollak MR, Delaney VB, Graham RM, Hebert SC. Gitelman's syndrome (Bartter's variant) maps to the thiazide-sensitive cotransporter gene locus on chromosome 16q13 in a large kindred. J Am Soc Nephrol 1996;7:2244-8.  Back to cited text no. 5
    
6.
Karolyi L, Ziegler A, Pollak M, Fischbach M, Grzeschik KH, Koch MC, et al. Gitelman's syndrome is genetically distinct from other forms of Bartter's syndrome. Pediatr Nephrol 1996;10:551-4.  Back to cited text no. 6
    
7.
Gesek FA, Friedman PA. Mechanism of calcium transport stimulated by chlorothiazide in mouse distal convoluted tubule cells. J Clin Invest 1992;90:429-38.  Back to cited text no. 7
    
8.
De Rouifignac C, Quamme G. Renal magnesium handling and its hormonal control. Physiol Rev 1994;74:305-22.  Back to cited text no. 8
    
9.
Zarraga Larrondo S, Vallo A, Gainza J, Muñiz R, Garcia Erauzkin G, Lampreabe I. Familial hypokalemia -hypomagnesemia or Gitelman's syndrome: A further case. Nephron 1992;62:340-4.  Back to cited text no. 9
    
10.
Shiah CJ, Tsai DM, Liao ST, Siauw CP, Lee LS. Acute muscular paralysis in an adult with subclinical Bartter's syndrome associated with gentamicin administration. Am J Kidney Dis 1994;24:932-5.  Back to cited text no. 10
    
11.
Cruz DN, Shaer AJ, Bia MJ, Lifton RP, Simon DB; Yale Gitelman's and Bartter's Syndrome Collaborative Study Group. Gitelman syndrome revisited: An evaluation of symptoms and health related quality of life. Kidney Int 2001;59:710-7.  Back to cited text no. 11
    
12.
Bettinelli A, Bianchetti MG, Giardin E, Caringella A, Cecconi M, Appiani AC, et al. Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis; Bartter and Gitelman syndromes. J Pediatr 1992;20:38-43.  Back to cited text no. 12
    
13.
Shaer AJ. Inherited primary renal tubular hypokalemic alkalosis: A review of Gitelman and Bartter syndromes. Am J Med Sci 2001;322:316-32.  Back to cited text no. 13
    
14.
Rodriguez-Soriano J. Bartter and related syndromes: The puzzle is almost solved. Pediatr Nephrol 1998;12:315-27.  Back to cited text no. 14
    
15.
Bettinelli A, Metta MG, Perini A, Basilico E, Santeramo C. Long-term follow up of a patient with Gitelman's syndrome. Pediatr Nephrol 1993;7:67-8.  Back to cited text no. 15
    




 

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