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]

  Paresthesias may be described, as well as weakness and fatigue that discourages the individuals from engaging in physical activity. [symptoma.com]

  Volume depletion is not as severe as in true Bartter syndrome, but patients can suffer from weakness, fatigue, dizziness, ataxia, and blurred vision. [wohproject.org]

• 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]

  Volume depletion is not as severe as in true Bartter syndrome, but patients can suffer from weakness, fatigue, dizziness, ataxia, and blurred vision. [wohproject.org]

• 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]

• 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]

• Low to Normal Blood Pressure

  Although people may initially have low or normal blood pressure, hypertension may develop in later life. Diagnosis Gitelman syndrome is diagnosed based on a physical examination, a review of symptoms, and the results of blood and urine analyses. [verywellhealth.com]

  […] pH in combination with low levels of chloride, potassium, and magnesium in the blood and decreased calcium excretion in the urine.[1] In contrast to people with Gordon's syndrome, those affected by Gitelman syndrome generally have low or normal blood [en.wikipedia.org]

  Bartter syndrome and Gitelman syndrome are autosomal recessive disorders of renal tubular electrolyte transport characterized by metabolic alkalosis, hypokalemia and low to normal blood pressure despite hyperaldosteronism and hyperreninemia. [clinicaladvisor.com]

• 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]

  Soc Nephrol, 2007, vol. 18 (pg. 1271 - 1283 ) 6, Qualitative Methods for Health Research, 2004 London, UK Sage 7 Early appearance of hypokalemia in Gitelman syndrome, Pediatr Nephrol, 2010, vol. 25 (pg. 2179 - 2182 ) 8 Self-management of chronic low back [academic.oup.com]

• Arm Weakness

  […] or tremor Occasional L arm weakness Episodes of R arm weakness Resting 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 [doi.org]

• 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]

  […] sports performance or endurance Episodes of fainting Cramps Muscle spasms Numbness or tingling (such as of the face) Growth delay Delayed puberty Short stature Excessive thirst Abdominal pain Adults with Gitelman syndrome may also experience dizziness, vertigo [rarediseases.info.nih.gov]

  Symptoms are weakness, vertigo, hypotension, tetany, paresthesias, abdominal pain, nausea, vomiting and fever. [thieme-connect.de]

• 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]

• Resting Tremor

  Occasional L arm weakness Episodes of R arm weakness Resting 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 [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]

[…] hyperkalaemic acidosis Recessive PHA1 is homozygous loss-of-function mutations, causing severe decompensation with minor illnesses Dominant PHA1 is heterozygous, causing milder disease Bartter syndrome Dysfunction of NKCC2, hence resembles effect of treatment [bigtomato.org]

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]

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]

Epidemiology Gitelman's syndrome is the most common renal tubular disorder among Caucasians (prevalence of 1 in 40,000). Most patients have onset of symptoms as adults, but some can present in childhood.[8] Bartter's syndrome is rare. [patient.info]

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]

Genetics), Clinical DNA Testing and DNA Banking - Marshfield, WI, USA TAT : 3-5 weeks price : $990.00 Gitelman Syndrome via the SLC12A3 Gene method(s): ◦ Sequencing, Next Gen PreventionGenetics (Prevention Genetics), Clinical DNA Testing and DNA Banking [genetests.org]

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2. Bettinelli A, Bianchetti MG, Girardin E. Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis: Bartter and Gitelman syndromes. Pediatr J. 1992;120:38–43.
3. Simon DB, Nelson-Williams C, Bia MJ. Gitelman's variant of Bartters syndrome, inherited hypokalemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Nature Genet. 1996;12:24–30.
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5. M Gjata, M Tase, A Gjata, and Zh Gjergji. Gitelman's Syndrome (Familial hypokalemia-hypomagnesemia). Hippokratia. 2007 Jul-Sep; 11(3): 150–153.
6. Riveira-Munoz E, Chang Q, Godefroid N, Hoenderop JG, Bindels RJ, Dahan K, Devuyst O. Belgian network for study of gitelman syndrome. Transcriptional and functional analyses of SLC12A3 mutations: new clues for the pathogenesis of Gitelman syndrome. J Am Soc Nephrol. 2007;1:1271–1283.
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.
8. Scognamiglio R, Negut C, Calò LA. Aborted sudden cardiac death in two patients with Bartter's/Gitelman's syndromes. Clin Nephrol. 2007;67:193–197.
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.