A novel compound heterozygous mutation in CYP11B2 (p.A153P and p.Q337*) associated with primary hypoaldosteronism

Congenital aldosterone synthase deficiency (ASD), a subset of primary hypoaldosteronism caused by CYP11B2 mutations, is characterized by hyponatremia, hyperkalemia, and elevated plasma renin (with normal cortisol production). This article focused on the clinical and genetic analysis of aldosterone synthase deficiency type II to achieve a deep understanding of the ASD pathophysiology.

The clinical biochemical data and whole exome genetic data of a newborn ASD patient were analyzed. The pathogenicity of the novel mutations was predicted using the Result Prediction Software (REVEL). Three-dimensional structures of the mutated gene coded protein was calculated. Steroid hormone level was measured by mass spectrometry. Literatures of all related reports were collected using the HGMD database and Pubmed to analyze the similarity and difference of the novel mutations.

The male neonate, born at 26⁺² weeks of gestation via emergency cesarean section, presented with poor respiratory function and low Apgar scores. Laboratory tests revealed severe hyponatremia, hyperkalemia, elevated plasma renin, and decreased cortisol levels. The mass spectrometry results indicated that the aldosterone level was very low. Two mutations in CYP11B2 gene were delected, including c.1009C > T and the novel mutation c.457G > C, with pathogenicity by affected protein structure and function. A total of 82 mutation sites including c.457G > C on CYP11B2 gene have been reported so far. The patient was treated with 9α-fluorohydrocortisone, and biochemical and plasma renin levels returned to normal after in 1 month. After 3 months, cortisol levels were normalized. The patient is currently under long-term follow-up.

Persistent hyponatremia necessitates thorough evaluation to rule out hypoaldosteronism, where genetic testing facilitates early definitive diagnosis. Long-term clinical follow-up remains critical for individualized treatment optimization. In this study, we reported the first identification of a novel CYP11B2 mutation (p.A153P) and confirmed its genetic association with the classic hypoaldosteronism phenotype, expanding the mutational spectrum of CYP11B2 and providing novel insights into the genetic basis of ASD. This newly identified mutation expands the spectrum of mutations in primary hypoaldosteronism.