Clinical and Genetic Analysis of a Korean Patient with Late-onset X-linked Adrenal Hypoplasia Congenita and Hypogonadotropic Hypogonadism: Identification of a Novel Mutation in the NR0B1 Gene

Abstract

Adrenal hypoplasia congenita (AHC) is caused by mutations in the NR0B1 gene on chromosome Xp21.3-p21.2. It manifests as X-linked primary adrenal failure in early infancy or childhood and as hypogonadotropic hypogonadism (HHG) at puberty. Although studies of AHC patients and mutations in the NR0B1 gene have been reported throughout the world, there has previously been only one other case report from Korea. We encountered a 23-year old Korean male with delayedonset AHC/HHG who had been previously diagnosed with adrenal insufficiency of unknown aetiology at age 13 years. Delayed puberty and incomplete HHG were observed. Direct sequencing of the NR0B1 gene revealed the patient to have a novel insertion mutation (c.959_960insT; Leu321ProfsX68). Although AHC is believed to be rare, it should be considered in a differential diagnosis of patients showing late-onset primary adrenal insufficiency.