Gitelman Syndrome: A Rare Cause of Persistent Hypokalemia

Gitelman syndrome is a rare autosomal recessive renal tubular disease, caused by mutations in the SLC12A3 gene, which encodes the renal thiazide-sensitive sodium-chloride cotransporter (NCCT) in the distal renal convoluted tubule. We present a 48-years-old male referred to our observation after being considered not suitable to a previous proposed surgery due to persistent hypokalemia. No valued symptoms were described. Laboratory tests showed metabolic alkalosis, hypomagnesemia, hypokalemia and secondary hyperaldosteronism. Genetic test was performed and sequence analysis of the SLC12A3 gene revealed a homozygous mutation confirming this disease. The aim of this report is to remind and increase awareness of the existence of GS, manage the condition properly and consider the risk of disease recurrence to the next generations.

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SUN-LB133 Analysis of Clinical Characteristics and Gene Mutation in Four Cases of Gitelman Syndrome

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1988 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Bin Yao

Keyword(s):

Gene Mutation ◽

Metabolic Alkalosis ◽

Clinical Characteristics ◽

Gene Mutations ◽

Gitelman Syndrome ◽

Compound Heterozygous ◽

Homozygous Mutation ◽

Slc12a3 Gene ◽

Renal Tubular Disorder ◽

Renal Tubular

Abstract Gitelman syndrome is an autosomal recessive renal tubular disorder characterized by renal salt wasting with secondary hyperreninemia and hyperaldosteronism, chronic hypokalemia with renal K wasting and metabolic alkalosis, and hypomagnesemia, and hypocalciuria. GS was found to be caused by mutations in SLC12A3 encoding the thiazide-sensitive sodium chloride cotransporter (NCCT) on the apical membrane of distal convoluted tubule. The prevalence worldwide is estimated at approximately 1:40,000, making it one of the most frequent inherited renal tubular disorders. To date, over 400 mutations scattered throughout SLC12A3 have been identified in GS patients. The majority of patients are compound heterozygous for SLC12A3 mutations, but a significant number of GS patients are found to carry only a single SLC12A3 mutation. The type of the SLC12A3 mutation may be a determinant factor in the severity of GS. The purpose of this study is to analyze clinical characteristics and gene mutation in four cases of GS. Methods: Four patients with closely resembling Gitelman syndrome was selected. Results: Six SLCl2A3 gene mutations were found in these four patients. There were one SLCl2A3 homozygous mutation in case 1 and case 3, and two SLCl2A3 heterozygous mutations in case 2 and case 4, respectively. This six gene mutations include missense mutations, frameshift mutations, and nonsense mutations. Four patients were diagnosed with Gitelman syndrome. Case 4 is the most severe with severe hypokalemia, accompanied by ventricular arrhythmias, which may be related to the presence of two SLC12A3 gene mutations in the patient. Conclusions: Four patients in this study were diagnosed with Gitelman syndrome based on their clinical characteristics and genetic testing results. For patients with hyperreninemia and hyperaldosteronism, chronic hypokalemia with renal K wasting and metabolic alkalosis, and hypomagnesemia, and hypocalciuria need to exclude Gitelman syndrome. Key words: Gitelmen Syndrome, Mutations, SlC12A3 gene

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Novel SLC12A3 mutation in Gitelman syndrome

BMJ Case Reports ◽

10.1136/bcr-2020-238097 ◽

2021 ◽

Vol 14 (1) ◽

pp. e238097

Author(s):

Rita Veríssimo ◽

Luís Leite de Sousa ◽

Tiago J Carvalho ◽

Pedro Fidalgo

Keyword(s):

Metabolic Alkalosis ◽

Autosomal Recessive ◽

Novel Mutation ◽

Gene Mutations ◽

Urinary Calcium ◽

Gitelman Syndrome ◽

Renal Ultrasound ◽

Calcium Excretion ◽

Slc12a3 Gene ◽

Specific Symptoms

Gitelman syndrome (GS) is an autosomal recessive disease characterised by the presence of hypokalaemic metabolic alkalosis with hypomagnesaemia and hypocalciuria. The prevalence of this disease is 1–10/40 000. GS is usually associated with mild and non-specific symptoms and many patients are only diagnosed in adulthood. The disease is caused by mutations in the SLC12A3 gene. We present the case of a 49-year-old man referred to a nephrology appointment due to persistent hypokalaemia and hypomagnesaemia. Complementary evaluation revealed hypokalaemia, hypomagnesaemia, metabolic alkalosis, hyperreninaemia, increased chloride and sodium urinary excretion, and reduced urinary calcium excretion. Renal function, remainder serum and urinary ionogram, and renal ultrasound were normal. A diagnosis of GS was established and confirmed with genetic testing which revealed a novel mutation in SLC12A3 (c.1072del, p.(Ala358Profs*12)). This novel mutation extends the spectrum of known SLC12A3 gene mutations and further supports the allelic heterogeneity of GS.

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Management of childhood Gitelman syndrome: a case study

Paediatrica Indonesiana ◽

10.14238/pi56.3.2016.184-91 ◽

2016 ◽

Vol 56 (3) ◽

pp. 184

Author(s):

Risky Vitria Prasetyo ◽

Putu Dian Saraswati ◽

Ninik Asmaningsih Soemyarso ◽

Mohammad Sjaifullah Noer

Keyword(s):

Autosomal Recessive ◽

Sudden Cardiac Arrest ◽

Local Heat ◽

Gitelman Syndrome ◽

Salt Wasting ◽

Adult Age ◽

The Face ◽

Males And Females ◽

Renal Tubular

Gitelman syndrome is a rare, autosomal recessive, renal tubular salt wasting disorder characterized by hypokalemia, and metabolic alkalosis in combination with significant hypomagnesemia and hypocalciuria.1,2 The prevalence is estimated to be 1 in 40,000 individuals. The condition affects both males and females of all ethnic backgrounds. The prevalence of heterozygotes is approximately 1% in Caucasian populations.2,3In the majority of cases, symptoms do not appear before the age of six years and the disease is usually diagnosed during adolescence or adulthood. Symptoms, such as transient episodes of muscle weakness and tetany, sometimes accompanied by abdominal pain, vomiting and fever, are often seen in Gitelman syndrome patients. Paresthesias, especially in the face, frequently occur. Remarkably, some patients are completely asymptomatic except for the appearance of chondrocalcinosis at adult age that causes swelling, local heat, and tenderness over the affected joints. Blood pressure is lower than that in the general population. Sudden cardiac arrest has been reported occasionally. In general, growth is normal but can be delayed in those Gitelman syndrome patients with severe hypokalemia and hypomagnesemia.2,4

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Glomerular podocyte dysfunction in inherited renal tubular disease

World Journal of Pediatrics ◽

10.1007/s12519-021-00417-0 ◽

2021 ◽

Author(s):

Li-Min Huang ◽

Jian-Hua Mao

Keyword(s):

Morphological Changes ◽

Clinical Signs ◽

Gitelman Syndrome ◽

Dent Disease ◽

Tubular Damage ◽

Electrolyte Disturbances ◽

Glomerular Lesions ◽

Glomerular Involvement ◽

Renal Tubular ◽

Renal Tubular Disease

Abstract Background Hereditary renal tubular disease can cause hypercalciuria, acid-base imbalance, hypokalemia, hypomagnesemia, rickets, kidney stones, etc. If these diseases are not diagnosed or treated in time, they can cause kidney damage and electrolyte disturbances, which can be detrimental to the maturation and development of the child. Glomerular involvement in renal tubular disease patients has only been considered recently. Methods We screened 71 papers (including experimental research, clinical research, etc.) about Dent’s disease, Gitelman syndrome, and cystinosis from PubMed, and made reference. Results Glomerular disease was initially underestimated among the clinical signs of renal tubular disease or was treated merely as a consequence of the tubular damage. Renal tubular diseases affect glomerular podocytes through certain mechanisms resulting in functional damage, morphological changes, and glomerular lesions. Conclusions This article focuses on the progress of changes in glomerular podocyte function in Dent disease, Gitelman syndrome, and cystinosis for the purposes of facilitating clinically accurate diagnosis and scientific treatment and improving prognosis.

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Gitelman Syndrome: A Rare Case of Hypokalaemia and a Novel Mutation

European Journal of Case Reports in Internal Medicine ◽

10.12890/2021_002182 ◽

2021 ◽

Author(s):

Maria Clara Novais de Matos ◽

Fábio Correia ◽

Maria Inês Silva ◽

Sofia Carola ◽

Ana Órfão ◽

...

Keyword(s):

Genetic Testing ◽

Sodium Chloride ◽

Metabolic Alkalosis ◽

Rare Case ◽

Novel Mutation ◽

Gitelman Syndrome ◽

Clinical Approach ◽

Slc12a3 Gene ◽

Sodium Chloride Cotransporter ◽

Renal Tubulopathy

Gitelman syndrome (GS) is a hereditary renal tubulopathy caused by mutations in the SLC12A3 gene which encodes the thiazide-sensitive apical sodium-chloride cotransporter. GS is characterized by hypokalaemia, hypomagnesaemia and metabolic alkalosis. Treatment is based on potassium and magnesium replacement ad eternum. We present the case of a young man with palpitations and persistent hypokalaemia, who was diagnosed with GS. Genetic testing revealed 2 mutations in the gene SLC12A3 of combined heterozygosity, both considered pathological. Interestingly, 1 of these mutations was not yet described in the literature or in the reviewed databases. We also discuss the clinical approach and the specificities of managing this rare hereditary renal tubulopathy.

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Acute pseudogout – Measure serum magnesium

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563219826169 ◽

2019 ◽

Vol 56 (3) ◽

pp. 411-414

Author(s):

RM Gama ◽

N Barkham ◽

J Ward ◽

R Gama ◽

I Borovickova

Keyword(s):

Metabolic Disease ◽

Serum Magnesium ◽

Left Knee ◽

Gitelman Syndrome ◽

Homozygous Mutation ◽

Younger Patients ◽

Slc12a3 Gene

We report a 49-year-old woman with an acute swollen left knee due to acute pseudogout with chondrocalcinosis as a presenting feature of Gitelman syndrome due a novel homozygous mutation of the SLC12A3 gene. This report highlights the under-recognized importance of excluding metabolic disease, including Gitelman syndrome, in younger patients whose sole presenting feature may be chondrocalcinosis with or without pseudogout, as this may impact on management and risk of further episodes. We also suggest that chondrocalcinosis and hypomagnesaemia with or without hypokalaemia are diagnostic of Gitelman syndrome.

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Investigation of Vestibular Function in Adult Patients with Gitelman Syndrome: Results of an Observational Study

Journal of Clinical Medicine ◽

10.3390/jcm9113790 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3790

Author(s):

Mihaela Alexandru ◽

Marie Courbebaisse ◽

Christine Le Pajolec ◽

Adeline Ménage ◽

Jean-François Papon ◽

...

Keyword(s):

Vestibular Function ◽

Head Rotation ◽

Gitelman Syndrome ◽

Head Impulse Test ◽

Caloric Test ◽

Vestibular Disorder ◽

Gene Encoding ◽

Slc12a3 Gene ◽

Sodium Chloride Cotransporter ◽

Kinetic Test

Gitelman syndrome (GS) is a rare salt-losing tubulopathy caused by an inactivating mutation in the SLC12A3 gene, encoding the thiazide-sensitive sodium chloride cotransporter (NCC). Patients with GS frequently complain of vertigo, usually attributed to hypovolemia. Because NCC is also located in the endolymphatic sac, we hypothesized that patients with GS might have vestibular dysfunction. Between April 2013 and September 2016, 20 (22%) out of 90 patients followed at the reference center complained of vertigo in the absence of orthostatic hypotension. Sixteen of them were referred to an otology department for investigation of vestibular function. The vertigo was of short duration and triggered in half of them by head rotation. Seven patients (44%) had a vestibular syndrome. Vestibular syndrome was defined: (1) clinically, as nystagmus triggered by the head shaking test (n = 5); and/or (2) paraclinically, as an abnormal video head impulse test (n = 0), abnormal kinetic test (n = 4) and/or abnormal bithermal caloric test (n = 3). Five patients had associated auditory signs (tinnitus, aural fullness or hearing loss). In conclusion, we found a high frequency of vestibular disorder in GS patients suffering from vertigo, suggesting a role of NCC in the inner ear. Referent physicians of these patients should be aware of this extrarenal manifestation that requires specific investigations and treatment.

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