Neglected Adrenal Hypoplasia Congenita in Two Siblings with Novel Genetic Mutations in NR0B1 Gene and Notable Clinical Course: A Case Report

Endocr Metab Immune Disord Drug Targets. 2024 Feb 21. doi: 10.2174/0118715303285405240202092244. Online ahead of print.


Background: Adrenal Hypoplasia Congenita (AHC) is a rare subtype of primary adrenal insufficiency (PAI) that can go undiagnosed easily. In this article, we report two brothers with hypogonadotropic hypogonadism and novel mutations in the NR0B1 gene who were misdiagnosed and mismanaged as having congenital adrenal hypoplasia (CAH) for several years.

Case presentation: Herein, we describe two brothers with similar histories; first, they were diagnosed with CAH and treated for that; however, after several years, they showed symptoms of lack of testosterone despite receiving CAH treatment. Low levels of testosterone and LH were detected in both, and a genetic test of CAH was negative for the first brother. Thereafter, DAX- 1 deficiency was suspected, and their genetic tests (the NR0B1 gene) confirmed the diagnosis of DAX-1.

Conclusion: The diagnosis of CAH in case of low levels of 17- OHP, testosterone, and LH, as well as central hypogonadotropic hypogonadism, should be studied, and further investigations are mandatory to evaluate other subtypes of PAI, especially AHC.

Keywords: Adrenal hyperplasia; DAX1.; NR0B1 gene; adrenal hypoplasia congenita; adrenal insufficiency; congenital; hypogonadotropic hypogonadism.

Publication types

  • Case Reports