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10.3390/jcm14134408
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Clinical and Biochemical Characteristics of Pseudohypoaldosteronism Type 1 with and Without Genetic Mutations: A Literature Review

by
Yuki Nakata
,
China Nagano
,
Yukihito Imagawa
,
Keisuke Shirai
,
Yu Masuda
,
Takumi Kido
,
Mariko Ashina
,
Kandai Nozu
and
Kazumichi Fujioka
*
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(13), 4408; https://doi.org/10.3390/jcm14134408
Submission received: 3 May 2025 / Revised: 16 June 2025 / Accepted: 20 June 2025 / Published: 20 June 2025
(This article belongs to the Section Endocrinology & Metabolism)
Versions Notes

Abstract

Background/Objectives: Pseudohypoaldosteronism type 1 (PHA-1) is a rare disorder characterized by aldosterone resistance, leading to hyponatremia, hyperkalemia, and elevated renin and aldosterone levels in neonates and infants. While genetic mutations in NR3C2 (mineralocorticoid receptor, MR) and SCNN1A/B/G (epithelial sodium channel, ENaC) are established causes of primary PHA-1, cases without detectable mutations have also been reported. This study aimed to compare the clinical characteristics of genetically confirmed PHA-1 cases—with or without mutations—and to assess genotype–phenotype correlations. Methods: A literature review was conducted using the Medline database, covering studies published from 1966 to October 2023. Included cases were diagnosed with PHA-1 and had undergone genetic testing for NR3C2 and SCNN1A/B/G. Clinical and biochemical data were compared across three groups: MR, ENaC, and non-mutation. Additional subgroup analysis based on mutation type (truncating vs. non-truncating) was also performed. Results: A total of 164 patients from 64 studies met the inclusion criteria. The ENaC group showed significantly higher serum potassium levels than the MR and non-mutation groups. Serum aldosterone levels were significantly higher in the MR group compared to the non-mutation group. A genotype–phenotype correlation was evident in the ENaC group, with truncating variants associated with more severe hyperkalemia. No such correlation was observed in the MR group. Conclusions: This review highlights distinct clinical features of PHA-1 according to genetic status. Aldosterone levels may aid in guiding decisions regarding genetic testing. Furthermore, variant type in ENaC-related PHA-1 may predict biochemical severity and should be considered in clinical management strategies.
Keywords: pseudohypoaldosteronism; renin; aldosterone; hyperkalemia; hyponatremia; mineralocorticoid receptor; epithelial sodium channel; MR; ENaC pseudohypoaldosteronism; renin; aldosterone; hyperkalemia; hyponatremia; mineralocorticoid receptor; epithelial sodium channel; MR; ENaC

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MDPI and ACS Style

Nakata, Y.; Nagano, C.; Imagawa, Y.; Shirai, K.; Masuda, Y.; Kido, T.; Ashina, M.; Nozu, K.; Fujioka, K. Clinical and Biochemical Characteristics of Pseudohypoaldosteronism Type 1 with and Without Genetic Mutations: A Literature Review. J. Clin. Med. 2025, 14, 4408. https://doi.org/10.3390/jcm14134408

AMA Style

Nakata Y, Nagano C, Imagawa Y, Shirai K, Masuda Y, Kido T, Ashina M, Nozu K, Fujioka K. Clinical and Biochemical Characteristics of Pseudohypoaldosteronism Type 1 with and Without Genetic Mutations: A Literature Review. Journal of Clinical Medicine. 2025; 14(13):4408. https://doi.org/10.3390/jcm14134408

Chicago/Turabian Style

Nakata, Yuki, China Nagano, Yukihito Imagawa, Keisuke Shirai, Yu Masuda, Takumi Kido, Mariko Ashina, Kandai Nozu, and Kazumichi Fujioka. 2025. "Clinical and Biochemical Characteristics of Pseudohypoaldosteronism Type 1 with and Without Genetic Mutations: A Literature Review" Journal of Clinical Medicine 14, no. 13: 4408. https://doi.org/10.3390/jcm14134408

APA Style

Nakata, Y., Nagano, C., Imagawa, Y., Shirai, K., Masuda, Y., Kido, T., Ashina, M., Nozu, K., & Fujioka, K. (2025). Clinical and Biochemical Characteristics of Pseudohypoaldosteronism Type 1 with and Without Genetic Mutations: A Literature Review. Journal of Clinical Medicine, 14(13), 4408. https://doi.org/10.3390/jcm14134408

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