Gitelman Syndrome: A Rare Cause of Seizure Disorder and a Systematic Review

Shahzad, Muhammad Asim; Mukhtar, Maryam; Ahmed, Asrar; Ullah, Waqas; Saeed, Rehan; Hamid, Mohsin

doi:https://doi.org/10.1155/2019/4204907

Case Reports in Medicine

On this page

Abstract Materials and Methods Case Presentation Results Discussion Conclusion Conflicts of Interest References Copyright Related Articles

Case Report | Open Access

Volume 2019 | Article ID 4204907 | https://doi.org/10.1155/2019/4204907

Gitelman Syndrome: A Rare Cause of Seizure Disorder and a Systematic Review

Muhammad Asim Shahzad,¹Maryam Mukhtar,²Asrar Ahmed,³Waqas Ullah,³Rehan Saeed,³and Mohsin Hamid³

Academic Editor: Masahiro Kohzuki

Received26 Aug 2018

Revised20 Nov 2018

Accepted17 Jan 2019

Published05 Feb 2019

Abstract

Gitelman syndrome is one of the few inherited causes of metabolic alkalosis due to salt losing tubulopathy. It is caused by tubular defects at the level of distal convoluted tubules, mimicking a thiazide-like tumor. It usually presents in late childhood or in teenage as nonspecific weakness, fatigability, polyuria, and polydipsia but very rarely with seizures. It is classically associated with hypokalemia, hypomagnesemia, hypocalciuria, hyperreninemia, and hyperaldosteronism. However, less frequently, it can present with normal magnesium levels. It is even rarer to find normomagnesemic patients of GS who develop seizures as the main complication since hypomagnesemia is considered the principal etiology of abnormal foci of seizure-related brain activity in GS cases. Interestingly, patients with GS are oftentimes diagnosed during pregnancy when the classic electrolyte pattern consistent with GS is noticed. Our case presents GS with normal serum magnesium in a patient, with seizures being the main clinical presentation. We also did a comprehensive literature review of 122 reported cases to show the prevalence of normal magnesium in GS cases and an overview of clinical and biochemical variability in GS. We suggest that further studies and in-depth analysis are required to understand the pathophysiology of seizures in GS patients with both normal and low magnesium levels.

1. Materials and Methods

Two different databases (PubMed and Scopus) were searched for all case reports and review articles previously published on GS syndrome. Moreover, after taking informed consent from our patient, we included data from the electronic medical record system to use this information for publication purposes.

2. Case Presentation

A 22-year-old female was brought to the hospital with the complaint of vomiting, generalized weakness, and two episodes of witnessed generalized tonic-clonic seizures 24 hours prior to the time of admission. She had about 5 episodes of nonbloody nonbilious vomiting. She was nonverbal at baseline but was reported to be more lethargic than usual and had a poor oral intake for the last 2 days and appeared to be in pain. Review of the system was negative for any previous episodes of seizures in the past, fever, diarrhea, abdominal pain, history of diuretic or laxative abuse, any periorbital puffiness, and extremities swelling. She was given lorazepam followed by successful resolution of seizures.

On physical examination, she was having borderline low blood pressure close to her baseline (105/56) with HR of 80, RR 18, O₂ sat. 100% on room air. Systemic examination was otherwise unremarkable without any overt signs of dehydration.

EKG showed U waves and nonspecific T wave changes. Pertinent labs showed serum blood urea nitrogen (BUN) and creatinine (Cr) of 16 and 0.77, respectively. Serum electrolytes showed serum sodium (Na) of 150 mEq/L, serum potassium (K) of 1.4 mEq/L, serum magnesium (Mg) of 2.8 mg/dL, and serum bicarbonate (HCO₃) of 35 mEq/L. Urine electrolytes included urine K 22 mEq/L, urine Na 121 mEq/L, and urine Cl 146 mEq/L. Her transtubular potassium gradient (TTKG) was 6.82. Complete blood count and liver function panel were within normal limits. Plasma renin activity (PRA) was 0.33 ng/ml/hr, serum aldosterone/K ratio of 1/1.4, and aldosterone/plasma renin ratio of 3. Differential included primary hyperaldosteronism, vomiting, and Bartter/Gitelman syndrome.

EEG showed abnormal epileptiform activity in the brain consistent with seizure. Low normal BP, high urine Cl with urine Ca, and history negative for laxative/diuretic intake made GS the more likely differential. Later on, biallelic identification of inactivating SLC12A3 mutation confirmed the diagnosis of GS.

Patient’s condition improved with aggressive K replenishment and antiepileptics in the medical ICU. She was later discharged in a medically stable condition and advised to follow-up with nephrologist and neurologist as an outpatient.

3. Literature Search

The available literature was systematically searched by three authors independently to retrieve all available material on variable clinical and metabolic presentations in Gitelman syndrome. There was no language filter placed, and articles were collected from their inception till May 2018, using the MEDLINE, Cochrane, Embase, and Scopus databases. Different MeSH terminologies such as “Gitelman,” “Gitelman syndrome,” “Gitelman disease,” and “GS” were combined using the Boolean operators “AND” and “OR” with the terms “hypomagnesemia,” “low magnesium,” “serum magnesium,” “plasma magnesium,” and “magnesium levels.” Another author collected few articles through manual search using the reference list of all retrieved publications through the aforementioned search strategy.

4. Results and Statistical Analysis

4.1. Literature Retrieval and the Results

After a thorough computer literature search, careful verification of references, and screening based upon the titles and abstracts, 122 cases of GS patients from 100 articles were identified for selection [1–100]. It was ensured that repetitive cases in these articles were excluded. Out of these 100 articles, data were also extracted from articles published in languages other than English.

4.2. Patients Description

There were a total of 122 patients including 45% () males and 65% () females. The age of female patients ranged from 4.8 months to 79 years (mean age 28.5 years), whereas for males, it ranged from 7 months to 80 years (mean age of 27.8 years). The description of patients included in this study is listed in Table 1.

4.3. Spectrum of Clinical Presentation and Associations

Clinical presentation of Gitelman syndrome was found to be highly variable in the reported patient population. About 30% () of the patients, including 14% () pregnant patients, were having nonspecific muscle cramps, weakness, fatigability, and anorexia, as the main presentation. These were likely due in part to hypokalemia and hypomagnesemia. About 12% () of the patients had extremities weakness out of which 7% () presented with bilateral lower limb weakness/paralysis and the rest of them had quadriplegia as initial presentation. Interestingly, 10.6% () of patients had perioral numbness and symptoms related to tetany/carpopedal spasm as first signs of Gitelman. About 6% of patients had polydipsia, polyuria/enuresis, and salt craving as presenting complaint; however, almost half of the total reported patients had some degree of polydipsia and polyuria in addition to main presenting clinical symptoms. Seven percent () of patients were completely asymptomatic and were diagnosed with routine lab work, either during routine clinical visits or perioperatively. Only 5.7% of patients () had GI-related issues such as anorexia, vomiting, constipation, abdominal pain, and weight loss as the main complaint. About 7 cases had no mention of the presenting complaints. Rest of the patients had their own unique features as seen in Table 1. Our patient had a unique presentation of generalized tonic-clonic seizure despite normal serum Mg levels, which has not been previously reported in the literature. GS was found to be most commonly associated with pseudogout and CPPD crystal deposition in about 10% of patients. Other associations included but not limited to Sjogren’s syndrome in 4%, chondrocalcinosis in 3%, and diabetes mellitus (both type 1 and type 2) and primary hyperaldosteronism in about 2% each. A less common association is seen with empty sella syndrome in 2 patients. Seizure disorder as a possible association with GS was previously reported in only one case by Beltagi et al., most likely due to hypomagnesemia [15]. Our patient, however, was unique with no prior history of epilepsy and had a seizure as the very first presentation with normal magnesium levels.

4.4. Complications Related to Gitelman Syndrome

Complications related to renal, cardiac, and endocrine systems have frequently been reported in the previous cases. Cardiac manifestations ranged from electrolytes related, asymptomatic ECG changes including prolonged Qtc, nonspecific T and U waves to pericardial effusion, and ventricular fibrillation. Reported renal pathologies included glomerulonephritides such as MPGN, FSGS, membranous nephropathy, and also cases of tubulointerstitial nephritis and renal tubular acidosis (RTA). Thyrotoxic periodic paralysis and hypokalemic periodic paralysis were also seen in a few cases. However, it must be noted that it is rare for two different renal entities to occur at the same time, and several of the studies did not confirm the diagnosis of GS by identifying the inactivation gene mutation leaving open the possibility that underlying pathology may not have been actually Gitelman’s. Long-term follow-up is usually required to observe for these complications; our patient, however, had no further follow-up in our hospital and was referred to the neurologist care.

4.5. Diagnosis and Management with Outcomes

Except for one case (), where there is no mention of the diagnostic method, genetic testing was utilized in 42% () cases, to definitively diagnose GS. The specific mutations to help make the diagnosis can be seen in Table 1. Almost 56% of patients () were diagnosed based on the presenting electrolytes abnormalities including serum and urine Na, K, Mg, and Ca used adjunctively with PAR concentration. Although the supportive testing with electrolytes and supplementary tests were highly suggestive of GS in these 68 cases, genetic tests were not done for various reasons. These included lack of resources, nonavailability of genetic test, and loss of follow-up by the patients to be the major ones.

Of note is the serum Mg level in the reported cases. Considering the normal range to be between 0.7 and 1 mmol/L (1.5–2 mEq/L; 1.7–2.4 mg/dL), 55% () patients had hypomagnesemia, i.e., <0.7 mmol/L, whereas 20% () had levels 0.7 mmol/L and above. In 31 cases, serum magnesium levels were not reported. These levels were important as the clinical severity of presentation was reflected by the degree of hypomagnesemia.

Electrolytes replacement, NSAIDs, and potassium-sparing diuretics with and without ACE In/ARB’s were the mainstay of treatment in almost all of the cases. Outcomes and prognosis were remarkable, and patients fully recovered from their acute presenting symptoms with exception of a few cases. These few cases reported persistent electrolytes abnormalities such as hypokalemia, metabolic alkalosis, hypomagnesemia, occasional paralysis and neurological symptoms, and treatment-related complications (indomethacin-related GI upset and bleeding). Recovery in the other cases is being defined as a sustained increase in electrolytes with magnesium >2, potassium >4, and significant improvement in the symptoms. Around 22% () cases did not comment on the outcomes.

5. Discussion

However, GS can also present with normal serum magnesium levels, and in one case, it has been reported to be in around 20–40% of GS cases [101]. From our review of around 122 cases, 20% () patients had serum magnesium levels >0.7 mmol/L. Both the groups of GS patients with normal and low magnesium levels largely stay asymptomatic and present later in life. Most present in teenage or adulthood with nonspecific generalized weakness or muscle cramps/fatigability, polyuria, and polydipsia [103]. However, seizure disorder has very rarely been reported as one of the main presenting complaints. Hypomagnesemia and metabolic alkalosis have been proposed as the pathophysiological basis of these rarely reported seizure disorders. Our case reports are unique in this sense that the patient of GS presented with seizure despite having normal serum magnesium levels. In our literature review, only one patient who was reported by Beltagi et al. [15] presented with somnolence and altered mental status and had a focal seizure as a complication. Even in that case, hypomagnesemia can be considered as the cause of epileptiform activity on EEG. This observation prompts us to consider causes other than hypomagnesemia as a culprit of seizure disorder, whenever evaluating the patient with GS. The final diagnosis of GS is based on the triad of clinical symptoms, biochemical abnormalities, and genetic testing [103]. Genetic testing is recommended for all patients, and the diagnosis is confirmed with the biallelic identification of inactivating SLC12A3 mutations [104]. We emphasize after this literature review that contrary to common clinical practice, overall clinical picture with more emphasis on genetic testing is a better strategy to clinch the diagnosis, and the diagnosis of GS can still be made even with normal serum magnesium levels.

5.1. Treatment

Most patients with GS remain untreated. The observation that chondrocalcinosis is due to magnesium deficiency argues clearly in favor of magnesium supplementation [15]. Most asymptomatic patients with GS remain untreated and undergo ambulatory monitoring, once a year, generally by nephrologists. Lifelong supplementation of magnesium and potassium is mandatory [105]. Cardiac workup should be performed to screen for risk factors of cardiac arrhythmias. All GS patients are encouraged to maintain a high-sodium diet. In general, the long-term prognosis of GS is excellent. Health education with annual regular nephrologist follow-up to evaluate for any developing complications seems to be a reasonable approach. As mentioned in the abstract, GS can be first identified during pregnancy when classic electrolyte abnormalities are noticed on the lab work [106]. Successful pregnancy is possible in majority of the patients; however, miscarriages have also been reported in the literature, which alludes to regular nephrologist follow-up during pregnancy.

6. Conclusion

(i)GS with variable biochemical presentation, i.e., normal serum magnesium level is a rare but potentially possible finding seen in various clinical settings(ii)Although exceedingly rare, seizure disorder can be the main clinical presentation of GS(iii)Causes other than low magnesium levels should be sought for the explanation of seizure disorder in GS(iv)Further studies are recommended to better understand the pathophysiology of abnormal epileptiform activity in GS(v)Successful pregnancy is possible in majority of the patients; however, miscarriages have also been reported in the literature, which alludes to regular nephrologist follow-up in the pregnant GS patient

Conflicts of Interest

The authors declare that they have no conflicts of interest.

References

C. Z. Molin and D. J. Trevisol, “Persistent severe hypokalemia: gitelman syndrome and differential diagnosis,” Jornal Brasileiro de Nefrologia, vol. 39, no. 3, pp. 337–340, 2017.
View at: Publisher Site | Google Scholar
X. Gu, Z. Su, M. Chen, Y. Xu, and Y. Wang, “Acquired Gitelman syndrome in a primary Sjögren syndrome patient with a SLC12A3 heterozygous mutation: a case report and literature review,” Nephrology, vol. 22, no. 8, pp. 652–655, 2017.
View at: Publisher Site | Google Scholar
C. J. Subasinghe, N. D. Sirisena, C Herath et al., “Novel mutation in the SLC12A3 gene in a Sri Lankan family with Gitelman syndrome & coexistent diabetes: a case report,” BMC Nephrology, vol. 18, no. 1, p. 140, 2017.
View at: Publisher Site | Google Scholar
Q. U. Mustafa, Z. H. Haroon, A. Ijaz, M. T. Sajid, and M. Ayyub, “Gitelman syndrome,” Journal of College of Physicians and Surgeons–Pakistan: JCPSP, vol. 27, no. 3, pp. 30–32, 2017.
View at: Google Scholar
T. Kusuda, T. Hosoya, T. Mori et al., “Acquired gitelman syndrome in an anti-SSA antibody-positive patient with a,” Internal Medicine, vol. 55, no. 21, pp. 3201–3204, 2016.
View at: Publisher Site | Google Scholar
S. M. Troster, J. E. Raizman, and L. Rubin, “An unusual case of gout in a young woman with gitelman syndrome,” Journal of Rheumatology, vol. 43, no. 11, pp. 2085–2087, 2016.
View at: Publisher Site | Google Scholar
K. Nozu, Y. Nozu, K Nakanishi et al., “Cryptic exon activation in SLC12A3 in Gitelman syndrome,” Journal of Human Genetics, vol. 62, no. 2, p. 335, 2017.
View at: Publisher Site | Google Scholar
Y. Zhang, F. Zhang, D Chen et al., “A novel homozygous mutation in the solute carrier family 12 member 3 gene in a Chinese family with Gitelman syndrome,” Brazilian Journal of Medical and Biological Research, vol. 49, no. 11, 2016.
View at: Publisher Site | Google Scholar
K. Gandhi, D. Prasad, V. Malhotra, and D. Agrawal, “Gitelman’s syndrome presenting with hypocalcemic tetany and hypokalemic periodic paralysis,” Saudi Journal of Kidney Diseases and Transplantation, vol. 27, no. 5, p. 1026, 2016.
View at: Publisher Site | Google Scholar
S. Skalova and S. Kutilek, “Transient hyperphosphatemia: a benign laboratory disorder in a boy with Gitelman syndrome,” Jornal Brasileiro de Nefrologia, vol. 38, no. 3, pp. 363–365, 2016.
View at: Publisher Site | Google Scholar
A. Zabotti, P. Della Siega, L. Picco, L. Quartuccio, M. Bassetti, and S. De Vita, “Gitelman syndrome disclosed by calcium pyrophosphate deposition disease: early diagnosis by ultrasonographic study,” Reumatismo, vol. 68, no. 1, pp. 53–55, 2016.
View at: Publisher Site | Google Scholar
S. Mukhopadhyay, S. Jana, A. Chatterjee, M. Roy, A. Sarkar, and J. Mukhopadhyay, “Quadriparesis due to Gitelman’s syndrome diagnosed with thiazide diuretic test response,” Saudi Journal of Kidney Diseases and Transplantation, vol. 27, no. 2, p. 407, 2016.
View at: Publisher Site | Google Scholar
L. Koudsi, S. Nikolova, and V. Mishra, “Management of a severe case of Gitelman syndrome with poor response to standard treatment,” BMJ Case Reports, vol. 2016, Article ID bcr2015212375, 2016.
View at: Publisher Site | Google Scholar
H. Akkari, M. Belkahla, M Youssef et al., “Pemphigus vegetans associated with Gitelman syndrome,” Indian Journal of Dermatology, Venereology, and Leprology, vol. 81, no. 6, p. 655, 2015.
View at: Publisher Site | Google Scholar
A. E. Beltagi, A. Norbash, and S. Vattoth, “Novel brain MRI abnormalities in Gitelman syndrome,” Neuroradiology Journal, vol. 28, no. 5, pp. 523–528, 2015.
View at: Publisher Site | Google Scholar
W. Wolyniec, S. Kaniuka-Jakubowska, M Nagel et al., “A case report of Gitelman syndrome resulting from two novel mutations in SLC12A3 gene,” Nefrología (English Edition), vol. 36, no. 3, pp. 304–309, 2016.
View at: Publisher Site | Google Scholar
Q. Lü, Y. Zhang, C Song et al., “A novel SLC12A3 gene homozygous mutation of Gitelman syndrome in an Asian pedigree and literature review,” Journal of Endocrinological Investigation, vol. 39, no. 3, pp. 333–340, 2016.
View at: Publisher Site | Google Scholar
D. R. Waguespack, R. Kasekar, K. Abdel-Kader, and R. B. Fissell, “Two cases of successful pregnancy in patients with Gitelman’s syndrome,” Clinical nephrology, vol. 84, no. 11, pp. 301–306, 2015.
View at: Publisher Site | Google Scholar
V. Martin-Miguel, M. A. Lafarga-Giribets, L. Garcia-Esteve, and M. D. Rodrigo-Claverol, “Casual diagnosis of Gitelman’s syndrome,” Semergen, vol. 40, no. 7, pp. e95–e98, 2014.
View at: Publisher Site | Google Scholar
M. Guedes-Marques, C. Silva, E. Ferreira, P. Maia, A. Carreira, and M. Campos, “Gitelman syndrome with hiponatremia, a rare presentation,” Nefrología (Madrid), vol. 34, no. 2, pp. 266–268, 2014.
View at: Google Scholar
N. Demoulin, S. Aydin, J. P Cosyns et al., “Gitelman syndrome and glomerular proteinuria: a link between loss of sodium-chloride cotransporter and podocyte dysfunction?” Nephrology Dialysis Transplantation, vol. 29, no. 4, pp. 117–120, 2014.
View at: Publisher Site | Google Scholar
M. Yoshihara, A. Sayo, M. Mayama, and H. Oguchi, “Pseudo gitelman syndrome associated with pregnancy,” Obstetrics & Gynecology, vol. 126, no. 4, pp. 877–880, 2015.
View at: Publisher Site | Google Scholar
K. Bouchireb, O. Boyer, L Mansour-Hendili et al., “Fanconi syndrome and severe polyuria: an uncommon clinicobiological presentation of a Gitelman syndrome,” BMC pediatrics, vol. 14, no. 1, p. 201, 2014.
View at: Publisher Site | Google Scholar
F. J. de Vargas Garcipérez, J. Mendoza, C. Ortiz, and P. Sánchez-Calderón, “Gitelman’s syndrome: a wolf in sheep’s clothing,” Revista Clinica Espanola, vol. 214, no. 4, pp. 229-230, 2014.
View at: Google Scholar
M. Brugnara, R. Gaudino, S Tedeschi et al., “Type III Bartter-like syndrome in an infant boy with Gitelman syndrome and autosomal dominant familial neurohypophyseal diabetes insipidus,” Journal of Pediatric Endocrinology and Metabolism, vol. 27, no. 9-10, pp. 971–975, 2014.
View at: Publisher Site | Google Scholar
A. Ş Koçkara, F. Candan, C. Hüzmeli, M. Kayataş, and D. Alaygut, “Gitelman’s syndrome associated with chondrocalcinosis: a case report,” Renal Failure, vol. 35, no. 9, pp. 1285–1288, 2013.
View at: Publisher Site | Google Scholar
E. Schneck, S. Schaumberg, C. Koch, M. Rickert, and C. Lichtenstern, “Anästhesiologisches management des Gitelman-syndroms anesthesiological management of Gitelman syndrome,” Der Anaesthesist, vol. 62, no. 9, pp. 728–733, 2013.
View at: Publisher Site | Google Scholar
B. Murienne, P. Pointet, and G. Beaune, “Gitelman syndrome: a crucial role of laboratory medicine for the diagnosis,” InAnnales de Biologie Clinique, vol. 71, no. 2, pp. 235–239, 2013.
View at: Google Scholar
P. Cotovio, C. Silva, N. Oliveira, and F. Costa, “Gitelman syndrome,” BMJ Case Reports, vol. 2013, Article ID bcr2013009095, 2013.
View at: Publisher Site | Google Scholar
G. Brambilla, M. Perotti, S. Perra, R. Dell’Oro, G. Grassi, and A. I. Pincelli, “It is never too late for a genetic disease: a case of a 79-year-old man with persistent hypokalemia,” Journal of Nephrology, vol. 26, no. 3, pp. 594–598, 2013.
View at: Publisher Site | Google Scholar
S. Mathen, M. Venning, and J. Gillham, “Outpatient management of Gitelman’s syndrome in pregnancy,” BMJ Case Reports, vol. 2013, Article ID bcr2012007927, 2013.
View at: Publisher Site | Google Scholar
A. J. Cruz and A. Castro, “Gitelman or bartter type 3 syndrome? A case of distal convoluted tubulopathy caused by CLCNKB gene mutation,” BMJ Case Reports, vol. 2013, Article ID bcr2012007929, 2013.
View at: Publisher Site | Google Scholar
A. Ali, Q. Masood, S. Yaqub, and W. Kashif, “A case of Gitelman syndrome with severe hyponatraemia and hypophosphataemia,” Singapore Medical Journal, vol. 54, no. 1, pp. 18–20, 2013.
View at: Publisher Site | Google Scholar
S. Skalova, D. Neuman, P. Lnenicka, and J. Stekrova, “Case report: gitelman syndrome as a cause of psychomotor retardation in a toddler,” Arab Journal of Nephrology and Transplantation, vol. 6, no. 1, pp. 37–39, 2013.
View at: Google Scholar
M. Yildiz, B. S. Yildiz, S. Karakoyun, S. Cakal, A. Sahin, and N. B. Aladag, “The effects of serum potassium and magnesium levels in a patient with Gitelman’s syndrome on the timing of ventricular wall motion and the pattern of ventricular strain and torsion,” Echocardiography, vol. 30, no. 2, pp. 47–50, 2013.
View at: Publisher Site | Google Scholar
S. K. Das, A. Ghosh, N. Banerjee, and S. Khaskil, “Gitelman’s syndrome presenting with hypocalcaemia, basal ganglia calcification and periodic paralysis,” Singapore Medical Journal, vol. 53, no. 10, pp. 222–224, 2012.
View at: Google Scholar
Ş Erten, G. G. Ceylan, and A. Altunoğlu, “Concomitance of Gitelman syndrome and familial mediterranean fever: a rare case presentation,” Renal Failure, vol. 34, no. 10, pp. 1333-1334, 2012.
View at: Publisher Site | Google Scholar
N. Takahashi, H. Kimura, S Mizuno et al., “Severe intraglomerular detachment of podocytes in a Gitelman syndrome patient,” Clinical and Experimental Nephrology, vol. 16, no. 3, pp. 495–500, 2012.
View at: Publisher Site | Google Scholar
A. M. Tomàs, A. R. Cid, C. C. Fernández, and J. C. Catalá, “Carpal arthritis as the initial manifestation of gitelman’s syndrome,” Reumatología Clínica (English Edition), vol. 8, no. 3, p. 159, 2012.
View at: Publisher Site | Google Scholar
Y. K. Wen, “An unusual case of Gitelman’s syndrome with hypercalcemia,” Renal Failure, vol. 34, no. 2, pp. 241–243, 2012.
View at: Publisher Site | Google Scholar
J. D. Farmer, G. M. Vasdev, and D. P. Martin, “Perioperative considerations in patients with Gitelman syndrome: a case series,” Journal of Clinical Anesthesia, vol. 24, no. 1, pp. 14–18, 2012.
View at: Publisher Site | Google Scholar
F. Nakhoul, N. Nakhoul, E. Dorman, L. Berger, K. Skorecki, and D. Magen, “Gitelman’s syndrome: a pathophysiological and clinical update,” Endocrine, vol. 41, no. 1, pp. 53–57, 2012.
View at: Publisher Site | Google Scholar
L. A. Calò and P. Caielli, “Gitelman’s syndrome and pregnancy: new potential pathophysiological influencing factors, therapeutic approach and materno-fetal outcome,” Journal of Maternal-Fetal & Neonatal Medicine, vol. 25, no. 8, pp. 1511–1513, 2012.
View at: Publisher Site | Google Scholar
A. Sinha, P. Lněnička, B. Basu, A. Gulati, P. Hari, and A. Bagga, “Gitelman syndrome: novel mutation and long-term follow-up,” Clinical and Experimental Nephrology, vol. 16, no. 2, pp. 306–309, 2012.
View at: Publisher Site | Google Scholar
J. G. Dis, “Pancreatic tumor and Gitelman syndrome,” Journal of Gastrointestinal and Liver Diseases, vol. 20, no. 3, pp. 329–332, 2011.
View at: Google Scholar
M. Biagioni, M. Marigliano, A Iannilli et al., “Diabetic ketoacidosis complicated with previously unknown Gitelman syndrome in a Tunisian child,” Diabetes Care, vol. 34, no. 6, p. 107, 2011.
View at: Publisher Site | Google Scholar
A. Azak, B. Huddam, G. Koçak, L. Ortabozkoyun, M. Uzel, and M. Duranay, “Gitelman syndrome complicated with dysglycemia,” Acta Diabetologica, vol. 48, no. 3, pp. 249-250, 2011.
View at: Publisher Site | Google Scholar
S. Ahmed, M. Qayyum, and F. Farooq, “Quadriparesis in an adult--Gitelman syndrome,” JPMA. Journal of Pakistan Medical Association, vol. 61, no. 2, pp. 182–184, 2011.
View at: Google Scholar
T. K. Kwan and M. C. Falk, “Second pregnancy outcome in a patient with Gitelman syndrome without the use of parenteral electrolyte supplementation,” Australian and New Zealand Journal of Obstetrics and Gynaecology, vol. 51, no. 1, pp. 94-95, 2011 1.
View at: Publisher Site | Google Scholar
C. S. Quinlan, J. C. Walsh, A. M. Moran, C. Moran, and S. K. O’Rourke, “Gitelman’s syndrome,” Journal of Bone and Joint Surgery. British, vol. 93, no. 2, pp. 266–268, 2011.
View at: Publisher Site | Google Scholar
S. K. Bandyopadhyay, S. Datt, S. K. Pal, and A. K. Saha, “Gitelman’s syndrome: a differential diagnosis of normocalcemic tetany,” Journal of Association of Physicians of India, vol. 58, p. 395, 2010.
View at: Google Scholar
R. Enriquez, V. Adam, A. E. Sirvent, A. B. García-García, I. Millán, and F. Amorós, “Gitelman syndrome due to p. A204T mutation in CLCNKB gene,” International Urology and Nephrology, vol. 42, no. 4, pp. 1099–1102, 2010.
View at: Publisher Site | Google Scholar
O. Hinschberger, L. Martzolff, G. Ioannou, D. Baumann, F. Jaeger, and P. Kieffer, “Acquired Gitelman syndrome associated with Sjögren’s syndrome and scleroderma,” La Revue de Medecine Interne, vol. 32, no. 8, pp. 96–98, 2011.
View at: Publisher Site | Google Scholar
S. Shanbhag, J. Neil, and C. Howell, “Anaesthesia for caesarean section in a patient with Gitelman’s syndrome,” International Journal of Obstetric Anesthesia, vol. 19, no. 4, pp. 451–453, 2010.
View at: Publisher Site | Google Scholar
M. Ceri, S. Unverdi, M Altay et al., “Focal segmental glomerulosclerosis in association with Gitelman syndrome,” International Urology and Nephrology, vol. 43, no. 3, pp. 905–907, 2011.
View at: Publisher Site | Google Scholar
N. Lakhi, J. Jones, and A. Govind, “Fetal demise despite normalisation of serum potassium in Gitelman syndrome case report and literature review,” Australian and New Zealand Journal of Obstetrics and Gynaecology, vol. 50, no. 3, pp. 301-302, 2010.
View at: Publisher Site | Google Scholar
F. Tammaro, A. Bettinelli, D Cattarelli et al., “Early appearance of hypokalemia in Gitelman syndrome,” Pediatric Nephrology, vol. 25, no. 10, pp. 2179–2182, 2010.
View at: Publisher Site | Google Scholar
T. Bansal, S. Abeygunasekara, and V. Ezzat, “An unusual presentation of primary renal hypokalemia–hypomagnesemia (Gitelman’s syndrome),” Renal Failure, vol. 32, no. 3, pp. 407–410, 2010.
View at: Publisher Site | Google Scholar
G. Daskalakis, S. Marinopoulos, A. Mousiolis, S. Mesogitis, N. Papantoniou, and A. Antsaklis, “Gitelman syndrome-associated severe hypokalemia and hypomagnesemia: case report and review of the literature,” Journal of Maternal-Fetal & Neonatal Medicine, vol. 23, no. 11, pp. 1301–1304, 2010.
View at: Publisher Site | Google Scholar
R. Bansal and V. K. Ranga, “Acquired Gitelman’s syndrome: an oxymoron?” International Urology and Nephrology, vol. 43, no. 1, pp. 233–236, 2011.
View at: Publisher Site | Google Scholar
F. P. McCarthy, C. N. Magee, W. D. Plant, and L. C. Kenny, “Gitelman’s syndrome in pregnancy: case report and review of the literature,” Nephrology Dialysis Transplantation, vol. 25, no. 4, pp. 1338–1340, 2010.
View at: Publisher Site | Google Scholar
H. Kumagai, S. Matsumoto, and K. Nozu, “Hypokalemic rhabdomyolysis in a child with Gitelman’s syndrome,” Pediatric Nephrology, vol. 25, no. 5, pp. 953–955, 2010.
View at: Publisher Site | Google Scholar
M. Gutierrez, F. Silveri, C Bertolazzi et al., “Gitelman syndrome, calcium pyrophosphate dihydrate deposition disease and crowned dens syndrome. A new association?” Rheumatology, vol. 49, no. 3, pp. 610–613, 2009.
View at: Publisher Site | Google Scholar
K. Nozu, K. Iijima, Y Nozu et al., “A deep intronic mutation in the SLC12A3 gene leads to Gitelman syndrome,” Pediatric Research, vol. 66, no. 5, pp. 590–593, 2009.
View at: Publisher Site | Google Scholar
Z. Miao, Y. Gao, R. J Bindels et al., “Coexistence of normotensive primary aldosteronism in two patients with Gitelman’s syndrome and novel thiazide-sensitive Na–Cl cotransporter mutations,” European Journal of Endocrinology, vol. 161, no. 2, pp. 275–283, 2009.
View at: Publisher Site | Google Scholar
N. Akhtar and F. Hafeez, “A rare case of Gitelman’s syndrome with hypophosphatemia,” Journal of the College of Physicians and Surgeons–Pakistan : JCPSP, vol. 19, pp. 257–259, 2009.
View at: Google Scholar
M. Roser, N. Eibl, B Eisenhaber et al., “Gitelman syndrome,” Hypertension, vol. 53, no. 6, pp. 893–897, 2009.
View at: Publisher Site | Google Scholar
G. de Arriba, M. Sánchez-Heras, and M. A. Basterrechea, “Gitelman syndrome during pregnancy: a therapeutic challenge,” Archives of Gynecology and Obstetrics, vol. 280, no. 5, pp. 807–809, 2009.
View at: Publisher Site | Google Scholar
T. Kasifoglu, A. Akalin, D. U. Cansu, and C. Korkmaz, “Hypokalemic paralysis due to primary hyperaldosteronism simulating Gitelman’s syndrome,” Saudi Journal of Kidney Diseases and Transplantation, vol. 20, no. 2, p. 285, 2009.
View at: Google Scholar
A. G. Pérez, T. Olea, C. Caramelo, E. Coto, and F. Santos, “Compound heterozygosis for intrón 9 + 1 G > T and Leu 850pro mutations in the SLC12A3 gene in Gitelman’s syndrome,” Nefrología, vol. 28, no. 6, 2008.
View at: Google Scholar
Y. K. Kim, H. C. Song, W. Y Kim et al., “Acquired Gitelman syndrome in a patient with primary Sjögren syndrome,” American Journal of Kidney Diseases, vol. 52, no. 6, pp. 1163–1167, 2008.
View at: Publisher Site | Google Scholar
J. de Haan, T. Geers, and A. Berghout, “Gitelman syndrome in pregnancy,” International Journal of Gynecology & Obstetrics, vol. 103, pp. 69–71, 2008.
View at: Publisher Site | Google Scholar
B. Akinci, A. Celik, F. Saygili, and S. Yesil, “A case of Gitelman’s syndrome presenting with extreme hypokalaemia and paralysis,” Experimental and Clinical Endocrinology & Diabetes, vol. 117, no. 02, pp. 69–71, 2009.
View at: Publisher Site | Google Scholar
K. Aoki, T. Tajima, Y Yabushita et al., “A novel initial codon mutation of the thiazide-sensitive Na-Cl cotransporter gene in a Japanese patient with Gitelman’s syndrome,” Endocrine Journal, vol. 55, no. 3, pp. 557–560, 2008.
View at: Publisher Site | Google Scholar
A. Morton, B. Panitz, and A. Bush, “Eplerenone for gitelman syndrome in pregnancy,” Nephrology, vol. 16, no. 3, p. 349, 2011.
View at: Publisher Site | Google Scholar
A. Volpe, P. Caramaschi, U Thalheimer et al., “Familiar association of Gitelman’s syndrome and calcium pyrophosphate dihydrate crystal deposition disease—a case report,” Rheumatology, vol. 46, no. 9, pp. 1506–1508, 2007.
View at: Publisher Site | Google Scholar
G. Ducarme, C. Davitian, M. Uzan, X. Belenfant, and C. Poncelet, “Pregnancy in a patient with Gitelman syndrome: a case report and review of literature,” Journal de Gynecologie, Obstetrique et Biologie de la Reproduction, vol. 36, no. 3, pp. 310–313, 2007.
View at: Publisher Site | Google Scholar
H. Kaito, K. Nozu, X. J. Fu et al., “Detection of a transcript abnormality in mRNA of the SLC12A3 gene extracted from urinary sediment cells of a patient with Gitelman’s syndrome,” Pediatric Research, vol. 61, no. 4, pp. 502–505, 2007.
View at: Publisher Site | Google Scholar
M. Sartori, E. Parotto, E Bonso et al., “Autonomic nervous system function in chronic hypotension associated with Bartter and Gitelman syndromes,” American Journal of Kidney Diseases, vol. 49, no. 2, pp. 330–335, 2007.
View at: Publisher Site | Google Scholar
N. Godefroid, E. Riveira-Munoz, C. Saint-Martin, M. C. Nassogne, K. Dahan, and O. Devuyst, “A novel splicing mutation in SLC12A3 associated with Gitelman syndrome and idiopathic intracranial hypertension,” American Journal of Kidney Diseases, vol. 48, no. 5, pp. 73–79, 2006.
View at: Publisher Site | Google Scholar
H. Y. Ng, S. H. Lin, C. Y. Hsu, Y. Z. Tsai, H. C. Chen, and C. T. Lee, “Hypokalemic paralysis due to Gitelman syndrome: a family study,” Neurology, vol. 67, no. 6, pp. 1080–1082, 2006.
View at: Publisher Site | Google Scholar
T. Hashida, M. Yamada, K Hashimoto et al., “Loss of consciousness and hypokalemia in an elderly man with a mutation of the thiazide-sensitive Na-Cl cotransporter gene,” Endocrine Journal, vol. 53, no. 6, pp. 859–863, 2006.
View at: Publisher Site | Google Scholar
C. Hanevold, A. Mian, and R. Dalton, “C1q nephropathy in association with Gitelman syndrome: a case report,” Pediatric Nephrology, vol. 21, no. 12, pp. 1904–1908, 2006.
View at: Publisher Site | Google Scholar
Y. T. Lee, I. F. Wang, T. H. Lin, and C. T. Huang, “Gitelman syndrome: report of three cases and literature review,” Kaohsiung Journal of Medical Sciences, vol. 22, no. 7, pp. 357–362, 2006.
View at: Publisher Site | Google Scholar
C. Schwarz, T. Barisani, E. Bauer, and W. Druml, “A woman with red eyes and hypokalemia: a case of acquired Gitelman syndrome “Rote Augen” and Hypokaliämie,” Wiener klinische Wochenschrift, vol. 118, no. 7-8, pp. 239–242, 2006.
View at: Publisher Site | Google Scholar
K. Panichpisal, F. Angulo-Pernett, S. Selhi, and K. M. Nugent, “Gitelman-like syndrome after cisplatin therapy: a case report and literature review,” BMC Nephrology, vol. 7, no. 1, p. 10, 2006.
View at: Publisher Site | Google Scholar
R. Gupta, V. Hu, T. Reynolds, and R. Harrison, “Sclerochoroidal calcification associated with Gitelman syndrome and calcium pyrophosphate dihydrate deposition,” Journal of Clinical Pathology, vol. 58, no. 12, pp. 1334-1335, 2005.
View at: Publisher Site | Google Scholar
J. A. Riancho, G. Saro, C. Sanudo, M. J. Izquierdo, and M. T. Zarrabeitia, “Gitelman syndrome: genetic and expression analysis of the thiazide-sensitive sodium-chloride transporter in blood cells,” Nephrology Dialysis Transplantation, vol. 21, no. 1, pp. 217–220, 2005.
View at: Publisher Site | Google Scholar
G. S. Talaulikar and M. C. Falk, “Outcome of pregnancy in a patient with Gitelman syndrome: a case report,” Nephron Physiology, vol. 101, no. 2, pp. 35–38, 2005.
View at: Publisher Site | Google Scholar
T. Ring, N. Knoers, M. S. Oh, and M. L. Halperin, “Reevaluation of the criteria for the clinical diagnosis of Gitelman syndrome,” Pediatric Nephrology, vol. 17, no. 8, pp. 612–616, 2002.
View at: Publisher Site | Google Scholar
T. Bourcier, P. Blain, P. Massin, J. P. Grünfeld, and A. Gaudric, “Sclerochoroidal calcification associated with Gitelman syndrome,” American Journal of Ophthalmology, vol. 128, no. 6, pp. 767-768, 1999.
View at: Publisher Site | Google Scholar
L. C. Liaw, K. Banerjee, and M. G. Coulthard, “Dose related growth response to indometacin in Gitelman syndrome,” Archives of Disease in Childhood, vol. 81, no. 6, pp. 508–510, 1999.
View at: Publisher Site | Google Scholar
A. Bettinelli, R. Rusconi, S Ciarmatori et al., “Gitelman disease associated with growth hormone deficiency, disturbances in vasopressin secretion and empty sella: a new hereditary renal tubular-pituitary syndrome?” Pediatric Research, vol. 46, no. 2, pp. 232–238, 1999.
View at: Publisher Site | Google Scholar
F. Ferraro, P. Debruxelles, A. Massard, B. Dorémus, and A. Blondiaux, “Gitelman syndrome: a rare cause of hypokalemia-hypomagnesemia in children,” Archives de Pediatrie: Organe Officiel de la Societe Francaise de Pediatrie, vol. 3, no. 3, pp. 293-294, 1996.
View at: Publisher Site | Google Scholar
Z. Dimitrijević, B. Mitić, and V. Đorđević, “Gitelman syndrome as a rare cause of hypokalemia: case report,” Acta Medica Medianae, vol. 53, no. 3, pp. 54–57, 2014.
View at: Publisher Site | Google Scholar
Y. Takeuchi, E. Mishima, H Shima et al., “Exonic mutations in the SLC12A3 gene cause exon skipping and premature termination in Gitelman syndrome,” Journal of American Society of Nephrology, vol. 26, no. 2, pp. 271–279, 2015.
View at: Publisher Site | Google Scholar
B. Zha, P. Zheng, J. Liu, and X. Huang, “Coexistence of graves’ disease in a 14-year-old young girl with gitelman syndrome,” Clinical Endocrinology, vol. 83, no. 6, pp. 995–997, 2015.
View at: Publisher Site | Google Scholar
J. Bolton and J. F. Mayhew, “Anesthesia in a patient with Gitelman syndrome,” Anesthesiology, vol. 105, no. 5, pp. 1064-1065, 2006.
View at: Publisher Site | Google Scholar
C. Li, X. Zhou, W Han et al., “Identification of two novel mutations in SLC12A3 gene in two Chinese pedigrees with Gitelman syndrome and review of literature,” Clinical Endocrinology, vol. 83, no. 6, pp. 985–993, 2015.
View at: Publisher Site | Google Scholar
F. Tosi, N. D. Bianda, A. C Truttmann et al., “Normal plasma total magnesium in Gitelman syndrome,” American Journal of Medicine, vol. 116, no. 8, pp. 573-574, 2004.
View at: Publisher Site | Google Scholar
M. Saeed, J. S. Bhandohal, P. Nepal, and S. Chaudhari, “Gitelman syndrome with a normal magnesium level,” Consultant, vol. 58, no. 6, p. 188, 2018.
View at: Google Scholar
I. Kurtz, J. J. Cohen, J. T. Harrington, N. E. Madias, and C. J. Zusman, “Molecular pathogenesis of Bartter’s and Gitelman’s syndromes,” Kidney International, vol. 54, no. 4, pp. 1396–1410, 1998.
View at: Publisher Site | Google Scholar
D. N. Cruz, A. J. Shaer, M. J. Bia, R. P. Lifton, and D. B. Simon, “Gitelman’s syndrome revisited: an evaluation of symptoms and health-related quality of life,” Kidney International, vol. 59, no. 2, pp. 710–717, 2001.
View at: Publisher Site | Google Scholar
W. Ji, J. N. Foo, B. J. O’Roak et al., “Rare independent mutations in renal salt handling genes contribute to blood pressure variation,” Nature Genetics, vol. 40, no. 5, pp. 592–599, 2008.
View at: Publisher Site | Google Scholar
L. Jiang, C. Chen, T Yuan et al., “Clinical severity of Gitelman syndrome determined by serum magnesium,” American Journal of Nephrology, vol. 39, no. 4, pp. 357–366, 2014.
View at: Publisher Site | Google Scholar
J. De Haan, T. Geers, and A. Berghout, “Gitelman syndrome in pregnancy,” International Journal of Gynecology & Obstetrics, vol. 103, no. 1, pp. 69–71, 2008.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2019 Muhammad Asim Shahzad et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

5463

Downloads

1429

Citations