A case report of neonatal pseudoaldosteronism caused by NR3C2 gene mutation

doi:10.3969/j.issn.1674-8115.2025.07.016

Abstract

Abstract:

Pseudohypoaldosteronism type Ⅰ (PHA Ⅰ) is a rare inherited disease, mainly caused by the deficiency of the aldosterone receptor or by reduced or absent binding between aldosterone and its receptor. It typically manifests as neonatal hyponatremia, hyperkalaemia, metabolic acidosis, accompanied by dehydration, vomiting, weight loss, and even shock. PHA Ⅰ is classified into renal-type with mutations in the salt corticosteroid receptor and multi-organ with mutations in any of the three subunits of the epithelial sodium channel (α, β or γ). The renal-type, which is inherited in an autosomal dominant manner, is caused by mutations in the aldosterone receptor with an isolated nephrogenic salt-loss syndrome, and the clinical symptoms are milder compared with those of the multi-organ type, which may improve with age. However, severity varies among individuals depending on the degree of salt loss, and if not treated in time, it may lead to shock due to repeated dehydration or even cardiac arrest due to high potassium. Currently, domestic studies have found that the human salt corticosteroid receptor is encoded by the NR3C2 gene, which is located between the regions of 4q31.1 and 4q31.2. This case reports a child with nephrogenic PHA Ⅰ due to a new-onset variant of the NR3C2 (4q31.22) gene, who had chromosomal anomalies in the fetus and demonstrated high blood pressure, high blood potassium and low sodium after birth. The diagnosis of renal neonatal PHA Ⅰ was confirmed by the presence of a microdeletion of NR3C2 gene (4q31.22 region) in the child, which was demonstrated by a genome-wide chromosomal assay and accompanied by a significant elevation of the plasma aldosterone level (>2 000 pg/mL), and by the presence of a microdeletion of NR3C2 gene (4q31.22 region) in the child. Electrolyte disorders were corrected after oral administration of concentrated sodium chloride, and the condition remained stable at the 1-month follow-up.

Key words: neonate, pseudohypoaldosteronism type Ⅰ (PHA Ⅰ), NR3C2 gene, hyperkalemia, hyponatremia

CLC Number:

R725.8

LI Junhe, ZHANG Rui, LIU Qingxu, SUI Sumin. A case report of neonatal pseudoaldosteronism caused by NR3C2 gene mutation[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(7): 934-938.

TrendMD

References 24

[1]	CHEEK D B, PERRY J W. A salt wasting syndrome in infancy[J]. Arch Dis Child, 1958, 33(169): 252-256.
[2]	KIM S J, PARK D, JANG W, et al. A neonate with autosomal dominant pseudohypoaldosteronism type 1 due to a novel microdeletion of the NR3C2 gene at 4q31.23[J]. Children (Basel), 2021, 8(12): 1090.
[3]	DELFORGE X, KONGOLO G, CAULIEZ A, et al. Transient pseudohypoaldosteronism: a potentially severe condition affecting infants with urinary tract malformation[J]. J Pediatr Urol, 2019, 15(3): 265.e1-265.e7.
[4]	RIEPE F G. Pseudohypoaldosteronism[J]. Endocr Dev, 2013, 24: 86-95.
[5]	AMIN N, ALVI N S, BARTH J H, et al. Pseudohypoaldosteronism type 1: clinical features and management in infancy[J]. Endocrinol Diabetes Metab Case Rep, 2013, 2013: 130010.
[6]	KAWASHIMA SONOYAMA Y, TAJIMA T, FUJIMOTO M, et al. A novel frameshift mutation in NR3C2 leads to decreased expression of mineralocorticoid receptor: a family with renal pseudohypoaldosteronism type 1[J]. Endocr J, 2017, 64(1): 83-90.
[7]	邹亮燕, 曾丽春, 蒋思远, 等. 多脏器型假性醛固酮减少症Ⅰ型1例并文献复习[J]. 中国循证儿科杂志, 2017, 12(5): 378-382.
	ZOU L Y, ZENG L C, JIANG S Y, et al. Multi-system pseudohypoaldosteronism type Ⅰ: a case report and literature review[J]. Chinese Journal of Evidence-Based Pediatrics, 2017, 12(5): 378-382.
[8]	YAMAZAKI O, ISHIZAWA K, HIROHAMA D, et al. Electrolyte transport in the renal collecting duct and its regulation by the renin-angiotensin-aldosterone system[J]. Clin Sci (Lond), 2019, 133(1): 75-82.
[9]	HANUKOGLU A. Type Ⅰ pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects[J]. J Clin Endocrinol Metab, 1991, 73(5): 936-944.
[10]	綦奕颖, 吴道奇. 44例假性醛固酮减少症Ⅰ型临床分析并文献复习[J]. 儿科药学杂志, 2021, 27(6): 14-17.
	QI Y Y, WU D Q. Clinical analysis of 44 cases of pseudoaldosteronism type Ⅰand literature review[J]. Journal of Paediatric Pharmacy, 2021, 27(6): 14-17.
[11]	NYSTRÖM A M, BONDESON M L, SKANKE N, et al. A novel nonsense mutation of the mineralocorticoid receptor gene in a Swedish family with pseudohypoaldosteronism type Ⅰ (PHA1)[J]. J Clin Endocrinol Metab, 2004, 89(1): 227-231.
[12]	AGARWAL R, KOLKHOF P, BAKRIS G, et al. Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine[J]. Eur Heart J, 2021, 42(2): 152-161.
[13]	BOWDEN S A, COZZI C, HICKEY S E, et al. Autosomal dominant pseudohypoaldosteronism type 1 in an infant with salt wasting crisis associated with urinary tract infection and obstructive uropathy[J]. Case Rep Endocrinol, 2013, 2013: 524647.
[14]	PALMER B F, CLEGG D J. Diagnosis and treatment of hyperkalemia[J]. Cleve Clin J Med, 2017, 84(12): 934-942.
[15]	KORKUT S, GÖKALP E, ÖZDEMIR A, et al. Dermal and ophthalmic findings in pseudohypoaldosteronism[J]. J Clin Res Pediatr Endocrinol, 2015, 7(2): 155-158.
[16]	杨汉华, 温丽华, 谢丽春, 等. SCNN1B基因突变致全身型假性醛固酮减少症1型1例报告并文献复习[J]. 临床儿科杂志, 2019, 37(8): 605-608.
	YANG H H, WEN L H, XIE L C, et al. Systemic pseudoaldosteronism type 1 caused by new mutation of SCNN1B gene and literature review[J]. Journal of Clinical Paediatrics, 2019, 37(8): 605-608.
[17]	KARACAN KÜÇÜKALI G, ÇETINKAYA S, TUNÇ G, et al. Clinical management in systemic type pseudohypoaldosteronism due to SCNN1B variant and literature review[J]. J Clin Res Pediatr Endocrinol, 2021, 13(4): 446-451.
[18]	ADACHI M, TAJIMA T, MUROYA K. Dietary potassium restriction attenuates urinary sodium wasting in the generalized form of pseudohypoaldosteronism type 1[J]. CEN Case Rep, 2020, 9(2): 133-137.
[19]	曹芯诚, 陈园园, 张可, 等. 新生儿多脏器型假性醛固酮减少症Ⅰ型[J]. 中国当代儿科杂志, 2023, 25(7): 774-778.
	CAO X C, CHEN Y Y, ZHANG K, et al. Neonatal systemic pseudohypoaldosteronism type Ⅰ [J]. Chinese Journal of Contemporary Paediatrics, 2023, 25(7): 774-778.
[20]	ESCOUBET B, COUFFIGNAL C, LAISY J P, et al. Cardiovascular effects of aldosterone: insight from adult carriers of mineralocorticoid receptor mutations[J]. Circ Cardiovasc Genet, 2013, 6(4): 381-390.
[21]	HANUKOGLU A, VARGAS-POUSSOU R, LANDAU Z, et al. Renin-aldosterone system evaluation over four decades in an extended family with autosomal dominant pseudohypoaldosteronism due to a deletion in the NR3C2 gene[J]. J Steroid Biochem Mol Biol, 2020, 204: 105755.
[22]	BOYANTON B L, ZARATE Y A, BROADFOOT B G, et al. NR3C2 microdeletions — an underrecognized cause of pseudohypoaldosteronism type 1A: a case report and literature review[J]. Lab Med, 2024, 55(5): 640-644.
[23]	COELHO ALMEIDA A, BASTOS GOMES M, MARTINS S A, et al. A case of severe systemic type 1 pseudohypoaldosteronism with 10 years of evolution[J]. J Pediatr Endocrinol Metab, 2022, 35(11): 1448-1452.
[24]	徐珍娥, 华子瑜, 朱珉, 等. 新生儿多脏器型醛固酮减少症Ⅰ型2例报告并文献复习[J]. 临床儿科杂志, 2020, 38(1): 56-60.
	XU Z E, HUA Z Y, ZHU M, et al. Multi-system pseudohypoaldosteronism type Ⅰ in neonates: a report of 2 cases and literature review[J]. Journal of Clinical Paediatrics, 2020, 38(1): 56-60.