Gitelman syndrome is a genetic condition that affects the renal tubules, leading to hypomagnesemia, hypokalemia and hypocalciuria, as well as acid-base imbalance (metabolic alkalosis). Although Gitelman syndrome was previously thought to be a milder form of a tubular transport disorder ascribed to Bartter syndrome, it is now recognized as a distinct medical entity that should not be confused with Bartter's syndrome [1] [2] [3] [4].

Gitelman syndrome is characterized by a wide variety of symptoms; not all patients experience the full spectrum. Diarrhea, vomiting and tetany, as a result of significant hypomagnesemia related to fluid loss, are some of the reported symptoms. Paresthesias may be described, as well as weakness and fatigue that discourages the individuals from engaging in physical activity. However, there have been cases reported that do not display serious symptoms; a young adult has been described in the literature as exhibiting only leg cramps, weakness, vomiting, and malaise [5]. Growth is hindered only in cases of profound hypomagnesemia and hypokalemia [6].

Some Gitelman syndrome patients may also report swollen, burning and tender joints; this is attributed to the chondrocalcinosis that may accompany the rest of the symptoms. Some isolated reports have described neurological symptoms such as ataxia, visual impairment and vertigo as well. As for the cardiovascular system, although Gitelman syndrome causes ventricular arrhythmias, they only rarely result in any considerable symptomatology, with only a few patients experiencing cardiac arrest [7] [8]. Patients are usually hypotensive.

• Weakness

  His mother had more slight symptoms of weakness than him with mild hypokalemia and hypocalciuria. Mild hypomagnesemia was also observed in his sister with occasional weakness. [ncbi.nlm.nih.gov]

• Fatigue

  Clinical signs are mostly secondary to chronic hypokalemia and include dizziness, fatigue, constipation and weakness. Patients can also present with muscle cramps, tetany, fatigue and convulsions due to severe metabolic alkalosis or hypomagnesemia. [ncbi.nlm.nih.gov]

• Chest Discomfort

  Both probands have normal or lower blood pressure, weakness and numbness of lower extremities, muscular soreness, and occasional palpitations and chest discomfort. Proband A wearies easily and Proband B has occasional joint numbness and pain. [ncbi.nlm.nih.gov]

• Recurrent Urinary Tract Infection

  The reason for their impaired renal function was not clear, but one participant had a history of recurrent urinary tract infections in the years following childbirth, necessitating pelvic floor surgery. [doi.org]

• Pseudotumor

  Three similar associations of Bartter syndrome/GS with pseudotumor cerebri were found in the literature, suggesting that electrolyte abnormalities and secondary aldosteronism may have a role in idiopathic intracranial hypertension. [ncbi.nlm.nih.gov]

• Back Pain

  She also had a history of NSAID use for chronic lower back pain caused by a previous sports injury. No participant reported any history of kidney stones, a common complication often associated with renal impairment. [doi.org]

  pain: an exploration of the impact of a patient-centered website, Patient Educ Couns, 2009, vol. 77 (pg. 27 - 32 ) 9 Online health information seeking in the context of the medical consultation in Switzerland, Qual Health Res, 2010, vol. 20 (pg. 1050 [academic.oup.com]

• Low Back Pain

  back pain: an exploration of the impact of a patient-centered website, Patient Educ Couns, 2009, vol. 77 (pg. 27 - 32 ) 9 Online health information seeking in the context of the medical consultation in Switzerland, Qual Health Res, 2010, vol. 20 (pg. [academic.oup.com]

• Heel Pain

  We report a case that has Gitelman syndrome (GS) and familial Mediterranean fever (FMF) presenting with recurrent arthritis of right knee and heel pain. Investigations showed hypokalemia and hypomagnesemia with urinary magnesium wasting. [ncbi.nlm.nih.gov]

• Psychomotor Retardation

  Here we describe a case of GS presenting in infancy with hypokalemia and psychomotor retardation. We present an 18-month-old boy who presented with psychomotor retardation and failure to thrive. [ncbi.nlm.nih.gov]

• Vertigo

  Despite symptoms including presyncope, vertigo, ataxia, and blurred vision, few data have been accumulated regarding formal cardiac evaluation for patients with Gitelman's syndrome. 3 We report a case of Gitelman's syndrome in a patient presenting with [nejm.org]

  Some isolated reports have described neurological symptoms such as ataxia, visual impairment and vertigo as well. [symptoma.com]

  In earlier clinical reports additional symptoms, such as ataxia, vertigo, and blurred vision have been reported. Cruz and colleagues have challenged the generally shared idea that GS is a mild disorder [ 3 ]. [ncbi.nlm.nih.gov]

  These symptoms include blurred vision, vertigo, and an impaired ability to coordinate voluntary movements (ataxia). A study from Yale indicated that Gitelman and Bartter syndrome have significant impact to quality of life (Cruz D et al., 2001). [rarediseases.org]

• Limb Weakness

  It was noted that in this pedigree, only the proband complained about recurrent episodes of bilateral lower limb weakness over 8 years, while his elder sister, mother and daughter did not present symptoms. [ncbi.nlm.nih.gov]

  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. [sjkdt.org]

• Papilledema

  She had bilateral papilledema, and right abducens palsy. CSF examination demonstrated high pressure (over 320 mmH(2)O) with normal cytochemistry. Brain MRI was normal. [ncbi.nlm.nih.gov]

• Resting Tremor

  tremor R arm Cramps Occasional Occasional leg cramps Occasional Polydipsia Drank   7 L/day, now 2 L 1 L daily, more with sport Yes (on diuretic) Vomiting During pregnancy During pregnancy During pregnancy Comorbidities Osteoarthritis IHD Hypertension [doi.org]

A detailed medical history, clinical examination and symptomatology, as well as laboratory testing are all used to diagnose Gitelman syndrome. Laboratory blood abnormalities include:

• Hypomagnesemia: less than 0.65 mmol/L
• Hypokalemia: between 2.3 and 3.1 mmol/L
• Hypocalciuria: less than 0.5 mg/kg/day

Although low serum magnesium and urine calcium had been regarded as a necessary part of the Gitelman syndrome diagnosis, a 2004 study reported two families with a valid diagnosis of Gitelman syndrome (corroborated by genetic tests), with women presenting with hypokalemia but normal urine calcium and serum magnesium [9]. The female patients of these families were also found to exhibit less severe hypokalemia and were generally asymptomatic. Patients with Gitelman syndrome tend to respond to diuretics, which suggests that the syndrome mainly affects the distal tubules. Genetic testing to confirm a diagnosis can be performed, if indicated. The gene involved is the SLC12A3 gene, encoding for the thiazide-sensitive NaCl cotransporter (NCC); the majority of patients affected by Gitelman syndrome exhibit SLC12A3 mutations. Genetic counseling is available for families affected by Gitelman syndrome.

Differential diagnosis should include Bartter's syndrome, laxative abuse and chronic vomiting. Other diagnostic modalities, such as electrocardiography or joint magnetic resonance imaging scans (MRI) can be employed depending on the symptoms reported by each individual.

• Hypouricemia

  A 6-year-old Caucasian girl was admitted via the Emergency department for vomiting, and initial laboratory investigations found hyponatremia, hypokalemia, metabolic acidosis with normal anion gap, hypophosphatemia, and hypouricemia. [ncbi.nlm.nih.gov]

Male patients tend to experience more severe symptoms and poor treatment effect. [ncbi.nlm.nih.gov]

In general, the long-term prognosis of GS is excellent. [ncbi.nlm.nih.gov]

Prognosis To date, there is no evidence that GS affects life expectancy. The documents contained in this web site are presented for information purposes only. [orpha.net]

Loss of function of mutated solute carrier family 12 member 3 (SLC12A3) gene is the most frequent etiology for Gitelman syndrome (GS), which is mainly manifested by hypokalemia, hypomagnesemia and hypocalciuria. [ncbi.nlm.nih.gov]

Etiology GS is caused by biallelic inactivating mutations in the SLC12A3 gene encoding the thiazide-sensitive sodium-chloride cotransporter NCC expressed in the apical membrane of cells lining the distal convoluted tubule. [orpha.net]

Our data suggested that BS or GS may contribute to the etiology of patients presented with hypertension and hypokalemia. Genetic testing for BS and GS pathogenic genes are recommended to facilitate precision diagnoses and targeted treatment. [tandfonline.com]

Summary Epidemiology Gitelman syndrome (GS) prevalence is estimated at 1 to 10 per 40,000 and potentially higher in Asia. GS is arguably the most frequent inherited tubulopathy. [orpha.net]

[…] potassium levels are not sufficiently replaced with replacement by mouth, aldosterone antagonists (such as spironolactone or eplerenone) or epithelial sodium channel blockers such as amiloride can be used to decrease urinary wasting of potassium.[1] Epidemiology [en.wikipedia.org]

Familial aggregation and genetic epidemiology of blood pressure. [dx.doi.org]

KEYWORDS: Acid–base; Electrolytes; Gitelman syndrome; Pathophysiology; Potassium [ncbi.nlm.nih.gov]

We review the molecular pathophysiology of Gitelman syndrome and related tubular disorders and discuss management in pregnancy. [scholars.northwestern.edu]

By taking the quite heterogeneous presentations and the apparently different pathophysiologies as the basis, the applicability of the physiologic classification has been tested. [journals.lww.com]

A pathophysiological and clinical uptodate. Endocrine 2012;41:53– [clinlabnavigator.com]

Prevention - Gitelman syndrome Not supplied. Diagnosis - Gitelman syndrome Not supplied. Prognosis - Gitelman syndrome Not supplied. Treatment - Gitelman syndrome Not supplied. Resources - Gitelman syndrome Not supplied. [checkorphan.org]

Hypomagnesemia is corrected with magnesium chloride (magnesium sulfate or oxide are avoided to prevent diarrhea) [ 7, 11 ]. Conclusion GS can present as early as two years of age. [jmedicalcasereports.biomedcentral.com]

It is therefore important to monitor patients and try to correct the potassium and magnesium disturbances to prevent acute exacerbations and progression 9. [f1000research.com]

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7. Foglia PEG, Bettineli A, Tosetto C, Cortesi C, Crosazzo L, Edefonti A, Bianchetti MG. Cardiac work up in primary hypokalemia-hypomagnesemia (Gitelman syndrome) Nephrol Dial Transplant. 2004;19:1398–1402.
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9. Lin SH, Cheng NL, Hsu YJ, Halperin ML. Intrafamiliar phenotype variability in patients with Gitelman syndrome having the same mutations in their thiazide-sensitive sodium/chloride cotransporter. Am J Kidney Dis. 2004;43:304–312.