Abstract

Background: X-linked adrenal hypoplasia congenita (X-AHC) is a hereditary disease caused by pathogenic NR0B1 variants which result in primary adrenal insufficiency and hypogonadotropic hypogonadism. We report four male patients diagnosed with X-AHC from three maternally-related families.
Method: Genetic testing used next-generation sequencing (Cases 1 and 3) or Sanger sequencing (Cases 2 and 4).
Results: All patients harbored a novel pathogenic variant of the NR0B1 gene (c.94_113del, p.Thr32Leufs*). Cases 1 and 2 displayed acute onset neonatal congenital adrenal insufficiency and had hypogonadotropic hypogonadism. In contrast, cases 3 and 4 experienced delayed adrenal insufficiency and demonstrated normal pubertal development.
Conclusions: Although pubertal development in X-AHC is diverse, reports of normal pubertal development are scarce. We report a novel NR0B1 variant with diverse manifestations.

DOI: 10.7754/Clin.Lab.2025.250326