假性醛固酮减少症

假性醛固酮减少症
	Ⅰ型假性醛固酮减少症患者体内醛固酮含量增多（醛固酮增多症），但身体对其无法作出反应，症状与醛固酮减少症相似
类型	renal tubular transport disease[*]
分类和外部资源
醫學專科	腎臟科
ICD-10	N25.8
eMedicine	924100
Orphanet	444916
	[编辑此条目的维基数据]

假性醛固酮减少症（pseudohypoaldosteronism，PHA），是一种症状类似醛固酮减少症的病症^[1]，系肇因于机体对醛固酮无法作出反应，负反馈调节抑制机制缺陷，导致醛固酮含量异常。

历史

1958年，Cheek和Perry首次描述了此种综合征^[2]。后来，儿科内分泌学家Aaron Hanukoglu称，假性醛固酮减少症有两种形态，遗传模式不同：一种是常染色体显性遗传的肾形态，主要表现为盐分自肾流失；另一种则是常染色体隐性遗传的多系统形态，表现为盐分自肾、肺、汗和唾液腺流失^[3]^[4]。此二种统称Ⅰ型假性醛固酮减少症。

醛固酮反应异常的遗传缺陷至少有以下两种可能：1.与醛固酮结合的盐皮质激素受体突变，或2.醛固酮所调节的基因突变。对Ⅰ型假性醛固酮减少症患者进行的分析排除了第一种可能性^[5]。后来，人们发现Ⅰ型假性醛固酮减少症是由基因SCNN1A、SCNN1B和SCNN1G突变导致的，这三个基因分别编码上皮钠通道亚基α、β和γ^[6]。

类型

类型	OMIM	基因	遗传	描述
PHA1A	177735	MLR	常染色体显性遗传	有钠流失
PHA1B	264350	SCNN1A、SCNN1B、SCNN1G	常染色体隐性遗传	有钠流失
PHA2	145260	WNK4、WNK1		无钠流失，可能与TRPV6有关^[7]

PHA2，即Ⅱ型假性醛固酮减少症，又名家族性高钾血症或戈登综合征，由Gordon于1986年首次描述，病因为潜在遗传缺陷导致肾脏远端小管氯化钠重吸收增加，进而导致体积膨胀、高血压、肾素水平降低。与Ⅰ型存在醛固酮抗性不同，Ⅱ型体积膨胀导致醛固酮水平降低。临床特征为高血压、高血钾、代谢性酸中毒（英语：metabolic acidosis），但肾功能正常^[8]。

治疗

Ⅰ型严重患者治疗需要较多氯化钠^[9]。相反，Ⅱ型患者需要限制盐分，并使用噻嗪利尿剂阻断氯化钠重吸收，使血压、血钾水平恢复正常。

参考资料

^ Pseudohypoaldosteronism: Overview - eMedicine Pediatrics: General Medicine. [2009-03-06]. （原始内容存档于2020-10-28）.
^ CHEEK DB, PERRY JW. A salt wasting syndrome in infancy.. Arch Dis Child. 1958, 33 (169): 252–6 [2020-12-18]. PMC 2012226 . PMID 13545877. doi:10.1136/adc.33.169.252. （原始内容存档于2020-11-11）.
^ Hanukoglu A. Type I pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects. The Journal of Clinical Endocrinology and Metabolism. Nov 1991, 73 (5): 936–44 [2019-09-20]. PMID 1939532. doi:10.1210/jcem-73-5-936. （原始内容存档于2019-10-03）.
^ Hanukoglu I, Hanukoglu A. Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases.. Gene. Jan 2016, 579 (2): 95–132. PMC 4756657 . PMID 26772908. doi:10.1016/j.gene.2015.12.061.
^ Chung E, Hanukoglu A, Rees M, Thompson R, Dillon M, Hanukoglu I, et al. Exclusion of the locus for autosomal recessive pseudohypoaldosteronism type 1 from the mineralocorticoid receptor gene region on human chromosome 4q by linkage analysis. J Clin Endocrinol Metab. 1995, 80 (11): 3341–5 [2020-12-18]. PMID 7593448. doi:10.1210/jcem.80.11.7593448. （原始内容存档于2020-11-11）.
^ Chang SS, Grunder S, Hanukoglu A, Rösler A, Mathew PM, Hanukoglu I, et al. Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. Nat Genet. 1996, 12 (3): 248–53 [2020-12-18]. PMID 8589714. doi:10.1038/ng0396-248. （原始内容存档于2020-11-11）.
^ Yang SS, Hsu YJ, Chiga M, Rai T, Sasaki S, Uchida S, Lin SH. Mechanisms for hypercalciuria in pseudohypoaldosteronism type II-causing WNK4 knock-in mice. Endocrinology. Apr 2010, 151 (4): 1829–36. PMID 20181799. doi:10.1210/en.2009-0951.
^ O'Shaughnessy, Kevin M. Gordon Syndrome: a continuing story. Pediatric Nephrology (Berlin, Germany). November 2015, 30 (11): 1903–1908 [2019-09-20]. ISSN 1432-198X. PMID 25503323. doi:10.1007/s00467-014-2956-7. （原始内容存档于2019-08-21）.
^ Hanukoglu A, Hanukoglu I. Clinical improvement in patients with autosomal recessive pseudohypoaldosteronism and the necessity for salt supplementation.. Clinical and Experimental Nephrology. 2010, 14 (5): 518–519. PMID 20661616. doi:10.1007/s10157-010-0326-8.

外部链接

[urlPseudohypoaldosteronism:_Overview_-_eMedicine_Pediatrics:_General_Medicine-1] Pseudohypoaldosteronism: Overview - eMedicine Pediatrics: General Medicine. [2009-03-06]. （原始内容存档于2020-10-28）.

[pmid13545877-2] CHEEK DB, PERRY JW. A salt wasting syndrome in infancy.. Arch Dis Child. 1958, 33 (169): 252–6 [2020-12-18]. PMC 2012226 . PMID 13545877. doi:10.1136/adc.33.169.252. （原始内容存档于2020-11-11）.

[pmid1939532-3] Hanukoglu A. Type I pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects. The Journal of Clinical Endocrinology and Metabolism. Nov 1991, 73 (5): 936–44 [2019-09-20]. PMID 1939532. doi:10.1210/jcem-73-5-936. （原始内容存档于2019-10-03）.

[2016-Hanukoglu-4] Hanukoglu I, Hanukoglu A. Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases.. Gene. Jan 2016, 579 (2): 95–132. PMC 4756657 . PMID 26772908. doi:10.1016/j.gene.2015.12.061.

[pmid7593448-5] Chung E, Hanukoglu A, Rees M, Thompson R, Dillon M, Hanukoglu I, et al. Exclusion of the locus for autosomal recessive pseudohypoaldosteronism type 1 from the mineralocorticoid receptor gene region on human chromosome 4q by linkage analysis. J Clin Endocrinol Metab. 1995, 80 (11): 3341–5 [2020-12-18]. PMID 7593448. doi:10.1210/jcem.80.11.7593448. （原始内容存档于2020-11-11）.

[pmid8589714-6] Chang SS, Grunder S, Hanukoglu A, Rösler A, Mathew PM, Hanukoglu I, et al. Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. Nat Genet. 1996, 12 (3): 248–53 [2020-12-18]. PMID 8589714. doi:10.1038/ng0396-248. （原始内容存档于2020-11-11）.

[Yang2010-7] Yang SS, Hsu YJ, Chiga M, Rai T, Sasaki S, Uchida S, Lin SH. Mechanisms for hypercalciuria in pseudohypoaldosteronism type II-causing WNK4 knock-in mice. Endocrinology. Apr 2010, 151 (4): 1829–36. PMID 20181799. doi:10.1210/en.2009-0951.

[8] O'Shaughnessy, Kevin M. Gordon Syndrome: a continuing story. Pediatric Nephrology (Berlin, Germany). November 2015, 30 (11): 1903–1908 [2019-09-20]. ISSN 1432-198X. PMID 25503323. doi:10.1007/s00467-014-2956-7. （原始内容存档于2019-08-21）.

[9] Hanukoglu A, Hanukoglu I. Clinical improvement in patients with autosomal recessive pseudohypoaldosteronism and the necessity for salt supplementation.. Clinical and Experimental Nephrology. 2010, 14 (5): 518–519. PMID 20661616. doi:10.1007/s10157-010-0326-8.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]