Novel non-stop variant of the NR0B1 gene in two siblings with adrenal hypoplasia congenita.

Objectives: Mutations in the dosage-sensitive sex reversal-AHC critical region on the X chromosome, gene 1 (DAX-1, officially NR0B1), cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG). Salt-losing adrenal insufficiency usually occurs during the neonatal period or early childhood. We report a novel non-stop variant of NR0B1 in two siblings and their unusual clinical course.

Case presentation: The proband was a boy who presented with an unusual form of AHC with neonatal onset of growth failure and mild salt loss, but without cutaneous pigmentation or plasma ACTH elevation. His 4-year-old elder brother had been growing healthily, but carried an AHC diagnosis. A non-stop variant of NR0B1 (p.*471K) was demonstrated in the patients and their mother.

Conclusions: We identified a novel non-stop variant of NR0B1 in two siblings. Mild salt loss associated with hyperkalemia is a crucial diagnostic clue for AHC, even without apparent symptoms of glucocorticoid deficiency.