Abstract: Hypokalemia is a common disorder in clinical settings; however, nonmolecular diagnostic testing cannot explain some causes of hypokalemia. To determine the etiology of clinically unexplained hypokalemia without hypertension (CUHypoNH) and to obtain a diagnostic yield of monogenic hypokalemia without hypertension in adults (MHNHA), we enrolled 82 patients with CUHypoNH for whole-exome sequencing or targeted gene sequencing of genes associated with 4000 monogenic disorders. Through molecular diagnosis, 25 patients were diagnosed with monogenic hypokalemia, and a diagnostic yield of 30.5% was obtained. Among patients with MHNHA, 18 patients (18/82, 22.0% and 72% of MHNHA) with Gitelman syndrome accounted for the largest proportion. Among the 29 diagnostic variants found, eight mutations have not been reported previously; these include three point mutations, one frameshift mutation, and four exon deletions. Based on the clinical presentation of patients with CUHypoNH, the diagnostic yield of monogenic hypokalemia was the highest for chronic asymptomatic hypokalemia (8/11, 72.7%). Twenty-one patients had concomitant hypomagnesemia, when accompanied with hypocalciuria, the molecular diagnostic yield of Gitelman syndrome increased to 88.2%. Overall, this study on hospitalized adult patients explored the etiology of CUHypoNH using high-throughput sequencing. Molecular diagnosis of CUHypoNH is clinically significant in guiding precision treatment and improving disease prognosis.
(© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
References: Jensen HK, Brabrand M, Vinholt PJ, Hallas J, Lassen AT. Hypokalemia in acute medical patients: risk factors and prognosis. Am J Med. 2015;128(1):60-67.
Eliacik E, Yildirim T, Sahin U, et al. Potassium abnormalities in current clinical practice: frequency, causes, severity and management. Med Princ Pract. 2015;24(3):271-275.
Lü Q, Dong Y, Wan H, et al. Consideration of the diagnosis of hypertension accompanied with hypokalaemia: monism or dualism? J Int Med Res. 2018;46(7):2944-2953.
Bao M, Cai J, Yang X, Ma W. Genetic screening for Bartter syndrome and Gitelman syndrome pathogenic genes among individuals with hypertension and hypokalemia. Clin Exp Hypertens. 2019;41(4):381-388.
Seys E, Andrini O, Keck M, et al. Clinical and genetic spectrum of Bartter syndrome type 3. J Am Soc Nephrol. 2017;28(8):2540-2552.
Weber F, Lehmann-Horn F. Hypokalemic periodic paralysis. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Mirzaa GM, Amemiya A, eds. GeneReviews. University of Washington; 2022.
Cheng CJ, Kuo E, Huang CL. Extracellular potassium homeostasis: insights from hypokalemic periodic paralysis. Semin Nephrol. 2013;33(3):237-247.
Fujimura J, Nozu K, Yamamura T, et al. Clinical and genetic characteristics in patients with Gitelman syndrome. Kidney Int Rep. 2019;4(1):119-125.
Conticini E, Negro A, Magnani L, et al. Gitelman syndrome associated with chondrocalcinosis and severe neuropathy: a novel heterozygous mutation in SLC12A3 gene. Reumatismo. 2020;72(1):67-70.
Gupta R, Hu V, Reynolds T, Harrison R. Sclerochoroidal calcification associated with Gitelman syndrome and calcium pyrophosphate dihydrate deposition. J Clin Pathol. 2005;58(12):1334-1335.
Blanchard A, Bockenhauer D, Bolignano D, et al. Gitelman syndrome: consensus and guidance from a kidney disease: improving global outcomes (KDIGO) controversies conference. Kidney Int. 2017;91(1):24-33.
Statland JM, Fontaine B, Hanna MG, et al. Review of the diagnosis and treatment of periodic paralysis. Muscle Nerve. 2018;57(4):522-530.
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