Liddle syndrome misdiagnosed as primary aldosteronism is caused by inaccurate aldosterone-rennin detection while a novel SCNN1G mutation is discovered

Abstract

Purpose

Through describing the confusing misdiagnosis process of Liddle syndrome, we try to reveal the importance of accurate aldosterone-renin detection and a genetic test for Liddle syndrome.

Methods

We found a family of hypertension and hypokalaemia with the proband of a 21-year-old female who had been misdiagnosed as primary aldosteronism (PA). She presented with high aldosterone and low renin levels. Aldosterone is not suppressed in the saline infusion test and captopril challenge test. However, treatment with a standard dose of spironolactone has no blood pressure improvement effect. A heterozygous variant of SCNN1G was found with whole exome sequencing and Liddle syndrome is indicated. Treatment with amiloride was effective. We rechecked aldosterone-renin levels with two different aldosterone and renin test kits. Clinical features and the mutant gene SCNN1G of each family member were determined by the Sanger method.

Results

The two kits had nearly opposite results. Among those Liddle syndrome patients confirmed by a genetic test, for Test kit A all ARR were screened positive while for test kit B negative. It seems Test kit B is consistent with the diagnosis while test kit A misleads the diagnosis. A novel SCNN1G mutation, c.1729 C > T, was found in this family, which introduce a premature stop codon in the γ subunit in the epithelial Na⁺ channel (ENaC) and resulted in a deletion of 72 amino acids at the carboxyl end.

Conclusion

inaccurate ARR detection might misdiagnose Liddle syndrome. A Gene test is an important method for the diagnosis of Liddle syndrome. A novel SCNN1G missense mutation, c.1729 C > T, is found in a Chinese family.

Keywords:

• Liddle syndrome
• primary aldosteronism
• SCNN1G
• aldosterone
• rennin

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Yaling Yang participated in data analysis and writing. Yaling Yang, Chenwei Wu, Duoduo Qu, Xinyue Xu participated in data sorting, genetic analysing and article manuscript. Lili Chen and Quanya Sun participated in data and sample collection. Xiaolong Zhao designed the study, participated and guided all stages of the study, discussed and revised the manuscript.

Additional information

Funding

Our research was supported by Shanghai Science and Technology Committee (21Y11904700) and Shanghai Municipal Health Commission (202140085).