Gitelman综合征继发横纹肌溶解症一例并文献复习

doi:10.16150/j.1671-2870.2023.02.012

摘要/Abstract

摘要：

Gitelman综合征（Gitelman syndrome, GS）是较少见的遗传性肾小管病，患者临床表现通常较轻，多为乏力、嗜盐、心悸等非特异性症状。GS继发横纹肌溶解症（rhabdomyolysis, RM）十分罕见，目前国内外文献报道仅10余例，且多见于儿童。本文报道了1例成人GS继发RM患者的详细诊治过程，并结合文献分析该疾病的诊治要点。该例患者为青年男性，长期存在不明原因的低钾血症，入院前因劳累出汗后，出现乏力加重伴肌肉酸痛。实验室检查提示患者存在低血钾、低血镁、代谢性碱中毒、低尿钙，肾素-血管紧张素-醛固酮系统轻度激活，伴肌酸激酶升高超过正常上限5倍。进一步行全外显子基因检测，结果提示该患者存在SLC12A3基因复合杂合突变，最终确诊该患者为GS继发RM。予口服安体舒通、氯化钾、钙镁片等补钾、补镁及水化治疗后，患者的临床症状明显好转。随访1年，患者的电解质水平基本正常，肾功能稳定。复习相关文献，发现GS患者继发RM临床罕见，且主要发生于严重低钾、低镁的儿童，常有剧烈运动、腹泻、服用药物等诱因，治疗不及时可出现肾功能衰竭等严重并发症。本病例提示成人GS患在一定诱因下亦可继发RM等严重症状,临床医师应掌握GS的诊治要点以减少漏诊、误诊。

关键词: Gitelman综合征, 横纹肌溶解症, 基因诊断, 文献复习

Abstract:

Gitelman syndrome (GS) is a hereditary renal tubular disease, with usually mild clinical manifestations and non-specific symptoms such as fatigue, salt craving, and palpitations. GS complicated with Rhabdomyolysis (RM) is very rare in clinical practice. To date, less than 20 cases were reported in the literature and most of them were children. Thus, we reported the detailed diagnosis and treatment process of an adult GS patient complicated with RM, and analyzed the main points of diagnosis and treatment in combination with literature. A young male patient with long-term hypokalemia of unknown etiology was hospitalized due to severe fatigue and muscle soreness after sweating. Laboratory examinations showed he had hypokalemia, hypomagnesium, metabolic alkalosis, low urinary calcium excretion, mild activation of the renin-angiotensin-aldosterone system (RAAS) and significantly increased serum creatine kinase. Compound heterozygous mutations were then detected in SLC12A3 gene by exome sequencing. He was finally diagnosed as GS complicated with RM. After taking oral spironolactone, potassium chloride, calcium magnesium tablets and hydration treatments, the patient's clinical symptoms improved significantly. His electrolyte level and renal function were stable during 1 year of follow-up. Literature review indicated that RM was a rare complication in GS patients that usually occurred in children with severe hypokalemia and hypomagnesia. It is often induced by intense exercise, diarrhea or medications and might cause renal acute failure without early diagnosis and proper treatments. This case suggests that adult patients with GS may also have serious symptoms such as RM under certain inducements. Clinicians should master the key points for the diagnosis and treatment of GS to reduce misdiagnosis.

Key words: Gitelman syndrome, Rhabdomyolysis, Genetic diagnosis, Literature review

中图分类号:

李丽娟, 谢洁, 张文, 马骏. Gitelman综合征继发横纹肌溶解症一例并文献复习[J]. 诊断学理论与实践, 2023, 22(02): 178-183.

LI lijuan, XIE Jie, ZHANG Wen, MA Jun. Gitelman syndrome complicated with rhabdomyolysis: a case report and literature review[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(02): 178-183.

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参考文献 29

[1]	中国研究型医院学会罕见病分会, 中国罕见病联盟, 北京罕见病诊疗与保障学会, 等. Gitelman综合征诊疗中国专家共识(2021版)[J]. 罕见病研究, 2022, 1(1):56-67.
	Rare Diseases Society of Chinese Research Hospital Association, China Alliance for Rare Disease, Beijing So-ciety of Rare Disease Clinical Care and Accessibility, Gitelman Syndrome Consensus Working Group. Expert consensus for the diagnosis and treatment of gitelman syndrome in China ( 2021)[J]. J Rare Dis, 2022, 1(1):56-67.
[2]	MELLI G, CHAUDHRY V, CORNBLATH D R. Rhabdomyolysis: an evaluation of 475 hospitalized patients[J]. Medicine (Baltimore), 2005, 84(6):377-385. doi: 10.1097/01.md.0000188565.48918.41 URL
[3]	BLANCHARD A, BOCKENHAUER D, BOLIGNANO D, et al. Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference[J]. Kidney Int, 2017, 91(1):24-33. doi: S0085-2538(16)30602-0 pmid: 28003083
[4]	HSU Y J, YANG S S, CHU N F, et al. Heterozygous mutations of the sodium chloride cotransporter in Chinese children: prevalence and association with blood pressure[J]. Nephrol Dial Transplant, 2009, 24(4):1170-1175. doi: 10.1093/ndt/gfn619 URL
[5]	KNOERS N V, LEVTCHENKO E N. Gitelman syndrome[J]. Orphanet J Rare Dis, 2008, 3:22. doi: 10.1186/1750-1172-3-22 pmid: 18667063
[6]	LI N, GU H F. Genetic and biological effects of SLC12A3, a sodium-chloride cotransporter, in gitelman syndrome and diabetic kidney disease[J]. Front Genet, 2022, 13:799224. doi: 10.3389/fgene.2022.799224 URL
[7]	GITELMAN综合征诊治专家共识协作组. Gitelman综合征诊治专家共识[J]. 中华内科杂志, 2017, 56(9):712-716.
	Gitelman Syndrome Collaboratwe Study Group. Expert consensus for the diagnosis and treatment of patients with Gitelman syndrome[J]. Chin J Intern Med, 2017, 56(9):712-716.
[8]	马骏, 任红, 谢静远, 等. Gitelman综合征47例临床特征分析[J]. 中国实用内科杂志, 2014, 34(3):273-276,280.
	MA J, REN H, XIE J Y, et al. Clinical features of patients with Gitelman syndrome[J]. Chin J Pract Intern Med, 2014, 34(3):273-276,280.
[9]	CABRAL B M I, EDDING S N, PORTOCARRERO J P, et al. Rhabdomyolysis[J]. Dis Mon, 2020, 66(8):101015. doi: 10.1016/j.disamonth.2020.101015 URL
[10]	SAURET J M, MARINIDES G, WANG G K. Rhabdo-myolysis[J]. Am Fam Physician, 2002, 65(5):907-912.
[11]	ZIMMERMAN J L, SHEN M C. Rhabdomyolysis[J]. Chest, 2013, 144(3):1058-1065. doi: S0012-3692(13)60626-1 pmid: 24008958
[12]	HE R, GUO W J, SHE F, et al. A rare case of hypokalemia-induced rhabdomyolysis[J]. J Geriatr Cardiol, 2018, 15(4):321-324. doi: 10.4067/S0034-98872014000500015 URL
[13]	[ LUZARDO L, SILVARIÑO R, BOGGIA J, et al. Severe hypokalemic rhabdomyolysis. Report of six cases[J]. Rev Med Chil, 2014, 142(5):651-655.
[14]	PECNIK P, MÜLLER P, VRABEL S, et al. Two cases of hypokalaemic rhabdomyolysis: same but different[J]. BMJ Case Rep, 2018, 2018:bcr2017223609.
[15]	VON VIGIER R O, ORTISI M T, LA MANNA A, et al. Hypokalemic rhabdomyolysis in congenital tubular disorders: a case series and a systematic review[J]. Pediatr Nephrol, 2010, 25(5):861-866. doi: 10.1007/s00467-009-1388-2 pmid: 20033223
[16]	NISHIHARA G, HIGASHI H, MATSUO S, et al. Acute renal failure due to hypokalemic rhabdomyolysis in Gitelman's syndrome[J]. Clin Nephrol, 1998, 50(5):330-332. pmid: 9840323
[17]	KUMAGAI H, MATSUMOTO S, NOZU K. Hypokalemic rhabdomyolysis in a child with Gitelman's syndrome[J]. Pediatr Nephrol, 2010, 25(5):953-955. doi: 10.1007/s00467-009-1412-6 pmid: 20072789
[18]	YANG L Y, YIN J H, YANG J, et al. Liquorice-induced severe hypokalemic rhabdomyolysis with Gitelman syndrome and diabetes: a case report[J]. World J Clin Cases, 2019, 7(10):1200-1205. doi: 10.12998/wjcc.v7.i10.1200 URL
[19]	XU J, HE J, XU S, et al. Gitelman syndrome with Graves' disease leading to rhabdomyolysis: a case report and lite-rature review[J]. BMC Nephrol, 2023, 24(1):123. doi: 10.1186/s12882-023-03180-8
[20]	MA J, REN H, LIN L, et al. Genetic features of Chinese patients with Gitelman syndrome: sixteen novel SLC12A3 mutations identified in a New Cohort[J]. Am J Nephrol, 2016, 44(2):113-121. doi: 10.1159/000447366 URL
[21]	LIU S, KE J, ZHANG B, et al. A novel compound heterozygous variant of SLC12A3 gene in a pedigree with Gitelman syndrome co-existent with thyroid dysfunction[J]. Endocr Pract, 2018, 24(10):889-893. doi: 10.4158/EP-2018-0218 URL
[22]	FUJIMURA J, NOZU K, YAMAMURA T, et al. Clinical and genetic characteristics in patients with Gitelman syndrome[J]. Kidney Int Rep, 2018, 4(1):119-125.
[23]	MIZOKAMI T, HISHINUMA A, KOGAI T, et al. Graves' disease and Gitelman syndrome[J]. Clin Endocrinol (Oxf), 2016, 84(1):149-150. doi: 10.1111/cen.12829 URL
[24]	CHANDRA A K, GOSWAMI H, SENGUPTA P. Effects of magnesium on cytomorphology and enzyme activities in thyroid of rats[J]. Indian J Exp Biol, 2014, 52(8):787-792. pmid: 25141541
[25]	MONCAYO R, MONCAYO H. The WOMED model of benign thyroid disease: Acquired magnesium deficiency due to physical and psychological stressors relates to dysfunction of oxidative phosphorylation[J]. BBA Clin, 2014, 3:44-64. doi: 10.1016/j.bbacli.2014.11.002 URL
[26]	周文华, 杨爱华, 牟利军. 四例Gitelman综合征继发横纹肌溶解综合征报告[J]. 中华急诊医学杂志, 2021, 30(4):500-503.
	ZHOU W H, YANG A H, MOU L J. Four cases of Stria-ted muscle tissue lysis syndrome secondary to Gitelman syndrome[J]. Chin J Emerg Med, 2021, 30(4):500-503.
[27]	石凯丽, 杜东海, 韩虹, 等. 儿童Gitelman综合征合并横纹肌溶解症一例并文献复习[J]. 中国药物与临床, 2019, 19(11):1886-1887.
	SHI K L, DU D H, HAN H, et al. A case of Gitelman syndrome with Rhabdomyolysis in children and literature review[J]. Chin Remedies Clin, 2019, 19(11):1886-1887.
[28]	彭稚媚, 莫南凤, 马明明, 等. Gitelman综合征纯合变异合并重度低钾血症一例[J]. 海南医学, 2019, 30(18):2437-2439.
	PENG Z M, MO N F, MA M M, et al. A case of homozygous variation with severe hypokalemia in Gitelman syndrome[J]. Hainan Med J, 2019, 30(18):2437-2439.
[29]	HUANG C L, KUO E. Mechanism of hypokalemia in magnesium deficiency[J]. J Am Soc Nephrol, 2007, 18(10):2649-2652. doi: 10.1681/ASN.2007070792 URL

项目	结果	参考范围
血钾（mmol/L）	1.7	3.5~5.5
血钠（mmol/L）	141	130~147
血氯（mmol/L）	102	96~108
血钙（mmol/L）	2.04	2~2.75
血镁（mmol/L）	0.52	0.74~1.03
血二氧化碳（mmol/L）	27.2	21.0~31.0
肌酐（μmol/L）	88	64~104
肌酸激酶（IU/L）	1 707	22~269
肌酸激酶同工酶（ng/mL）	38.1	0.3~4
肌红蛋白（ng/mL）	586.6	<70
肌钙蛋白I（ng/mL）	0.035	<0.040
血气分析
pH	7.453	7.350~7.450
PCO₂ （mmHg）	41.3	350~450
碳酸氢根（HCO₃^-）（mmol/L）	28.9	220~260
标准碱剩余（mmol/L）	4.9	-30~30
24 h尿电解质
尿钾（mmol/24 h）	110.40	36.00~90.00
尿钠（mmol/24 h）	584.20	137.00~257.00
尿钙（mmol/24 h）	1.9	2.5~7.5
尿镁（mmol/24 h）	8.74	3.00~5.00
尿氯（mmol/24 h）	685.40	170~250
尿钾排泄分数（%）	37	8~12
尿镁排泄分数（%）	17.1	<1.00
24 h尿肌酐（mmol/24 h）	8.62
尿钙/尿肌酐	0.22