title: Hypokalemic paralysis in a middle-aged female with classic Bartter syndrome.
abstract: Inherited classic Bartter syndrome (cBS) is an autosomal recessive renal tubular disorder resulting from inactivating mutations in the asolateral chloride channel (C1C-Kb) and usually presents in early infancy or childhood with mild to moderate hypokalemia. Profound hypokalemic paralysis in patients with cBS is extremely rare, especially in middle age. A 45-year-old Chinese female patient was referred for evaluation of chronic severe hypokalemia despite regular K+ supplementation (1 mmol/kg/d). She had had two episodes of muscle paralysis due to severe hypokalemia (K+ 1.9 - 2.1 mmol/l) in the past 3 years. She denied vomiting, diarrhea, or the use of laxatives or diuretics. Her blood pressure was normal. Biochemical studies showed hypokalemia (K+ 2.5 mmol/l) with renal potassium wasting, metabolic alkalosis (HCO3- 32 mmol/l), normomagnesemia (Mg2+ 0.8 mmol/l), hypercalciuria (calcium to creatinine ratio 0.5 mmol/mmol; normal < 0.22 mmol/mol), high plasma renin activity, but normal plasma aldosterone concentration. Abdominal sonography revealed neither renal stones nor nephrocalcinosis. Acquired causes of cBS such as autoimmune disease and drugs were all excluded. Molecular analysis of the CLCNKB gene, encoding ClC-Kb, and SLC12A3, encoding the thiazide-sensitive sodium chloride cotransporter (NCC), revealed compound heterozygous mutations in CLCNKB (L335P and G470E) inherited from her parents; her SLC12A3 was normal. These two mutations were not identified in 100 healthy subjects. Her plasma K+ concentration rose to 3 - 3.5 mmol/l after the addition of spironolactone. Inherited cBS may present with hypokalemic paralysis and should be considered in adult patients with hypokalemia and metabolic alkalosis.
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Chiang
authors.forename: Shih-Hung
authors.initials: SH
authors.lastname: Lin
authors.forename: Jenq-Shyong
authors.initials: JS
authors.lastname: Chan
authors.forename: Shih-Hua
authors.initials: SH
authors.lastname: Lin
mesh_terms: D001477:Bartter Syndrome / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D018118:Chloride Channels / Q000235:genetics; D019587:Dietary Supplements; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007008:Hypokalemia / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D008875:Middle Aged; D009154:Mutation; D010243:Paralysis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D010641:Phenotype; D011189:Potassium Chloride / Q000627:therapeutic use; D064486:Solute Carrier Family 12, Member 3 / Q000235:genetics; D013148:Spironolactone / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C412733:CLCNKB protein, human; D018118:Chloride Channels; D004232:Diuretics; C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3; D013148:Spironolactone; D011189:Potassium Chloride