Hypokalaemic paralysis and metabolic alkalosis in a patient with Sjögren syndrome: a case report and literature review.

BACKGROUND: Acquired Gitelman syndrome is a very rare disorder reported in association with autoimmune disorders, mostly Sjögren syndrome. It is characterized by the presence of hypokalaemic metabolic alkalosis, hypocalciuria, hypomagnesaemia and hyper-reninaemia, in the absence of typical genetic mutations associated with inherited Gitelman syndrome. CASE PRESENTATION: A 20 year old woman who was previously diagnosed with primary Sjögren syndrome and autoimmune thyroiditis presented with two week history of lower limb weakness and salt craving. Examination revealed upper limb and lower limb muscle weakness with muscle power of 3/5 on MRC scale and diminished deep tendon reflexes. On evaluation, she had hypokalaemia with high trans-tubular potassium gradient, metabolic alkalosis and hypocalciuria, features suggestive of Gitelman syndrome. New onset hypokalaemic alkalosis in a previously normokalaemic patient with Sjögren syndrome strongly favored a diagnosis of acquired Gitelman syndrome. Daily potassium supplementation and spironolactone resulted in complete clinical recovery. CONCLUSIONS: Acquired Gitelman syndrome associated with Sjögren syndrome is rare. It should be considered as a differential diagnosis during evaluation of acute paralysis and hypokalaemic metabolic alkalosis in patients with autoimmune disorders, especially Sjögren syndrome.

Systemic lupus erythematosus complicated by a Gitelman-like syndrome in an 8-year-old girl.

An 8-year-old girl with recently diagnosed Systemic Lupus Erythematosus (SLE) (class 4 lupus nephritis with autoimmune hemolytic anemia) presented to the pediatric nephrology clinic with polyuria, tiredness and cramps; laboratory investigations revealed refractory hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria and hyperchloriuria. There was no history of diuretic administration. These features were consistent with the Gitelman syndrome. She required large doses of potassium and magnesium supplementation along with spironolactone, for normalization of the serum potassium and magnesium levels. Immunosuppressive therapy was continued with cyclophosphamide pulses administered on a monthly basis. The doses of potassium and magnesium supplements were tapered off over the next 6 months. The clinical exome sequencing was negative for any mutations in the SLC12A3 gene. An 'acquired' form of Gitelman syndrome has been reported earlier in association with Sjogren syndrome and systemic sclerosis. Though tubular disorders such as renal tubular acidosis have been reported in association with SLE, a Gitelman-like syndrome has not been reported earlier. This case adds Gitelman-like tubulopathy to the clinical spectrum of tubular disorders complicating SLE.

Hypokalaemia and failure to thrive: report of a misleading onset.

AIM: We report a case of Gitelman Syndrome (GS) in a 9-year-old girl, previously diagnosed as a Bartter syndrome at one year of life. METHODS: She had been treated with potassium, for over 8 years and was admitted because of fatigue, numbness and weakness of both legs. The patient has typical laboratory findings, including hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria, thus GS was suspected. RESULTS: Genetic analysis was performed two mutations IVS9(+1)G>T were detected in the thiazide-sensitive Na-Cl cotransporter (TSC) gene (SLC12A3), thus she was diagnosed as having GS. She was treated with oral potassium and magnesium supplements with resolution of the symptoms. CONCLUSION: This case reminded us that doctors should be alert to the initial presentation of renal tubular diseases. Detailed electrolyte analysis, hormone evaluations and clinic follow-up are mandatory for their correct differential diagnosis.

Transcriptional and functional analyses of SLC12A3 mutations: new clues for the pathogenesis of Gitelman syndrome.

Gitelman syndrome (GS) is a recessive salt-losing tubulopathy that is caused by mutations in the SLC12A3 gene that encodes the sodium-chloride co-transporter (NCC). GS is characterized by significant inter- and intrafamilial phenotype variability, with early onset and/or severe clinical manifestations in some patients. No correlations between the disease variability and the position/nature of SLC12A3 mutations have been investigated thus far. In this study, extensive mutational analyses of SLC12A3 were performed in 27 patients with GS, including genomic DNA sequencing, multiplex ligation-dependent probe amplification, cDNA analysis, and quantification of allele-specific transcripts, in parallel with functional analyses in Xenopus laevis oocytes and detailed phenotyping. Twenty-six SLC12A3 mutations were identified in 25 patients with GS, including eight novel (detection rate 80%). Transcript analysis demonstrated that splicing mutations of SLC12A3 lead to frameshifted mRNA subject to degradation by nonsense-mediated decay. Heterologous expression documented a novel class of NCC mutants with defective intrinsic transport activity. A subgroup of patients presented with early onset, growth retardation, and/or detrimental manifestations, confirming the potential severity of GS. The mutations that were associated with a severe presentation were the combination at least for one allele of a missplicing resulting in a truncated transcript that was downregulated by nonsense-mediated decay or a nonfunctional, cell surface-absent mutant. The most recurrent mutation on the second allele was a newly described NCC mutant that affected the functional properties of the co-transporter. These data suggest that the nature/position of SLC12A3 mutation, combined with male gender, is a determinant factor in the severity of GS and provide new insights in the underlying pathogenic mechanisms of the disease.